Rationale: The current management of advanced non–small cell lung cancer (NSCLC) requires differentiation between squamous and nonsquamous subtypes as well as epidermal growth factor receptor (EGFR) mutation status. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is increasingly used for the diagnosis and staging of lung cancer. However, it is unclear whether cytology specimens obtained with EBUS-TBNA are suitable for the subclassification and genotyping of NSCLC.
Objectives: To determine whether cytology specimens obtained from EBUS-TBNA in routine practice are suitable for phenotyping and genotyping of NSCLC.
Methods: Cytological diagnoses from EBUS-TBNA were recorded from 774 patients with known or suspected lung cancer across five centers in the United Kingdom between 2009 and 2011.
Measurements and Main Results: The proportion of patients with a final diagnosis by EBUS-TBNA in whom subtype was classified was 77% (95% confidence interval [CI], 73–80). The rate of NSCLC not otherwise specified (NSCLC-NOS) was significantly reduced in patients who underwent immunohistochemistry (adjusted odds ratio, 0.50; 95% CI, 0.28–0.82; P = 0.016). EGFR mutation analysis was possible in 107 (90%) of the 119 patients in whom mutation analysis was requested. The sensitivity, negative predictive value, and diagnostic accuracy of EBUS-TBNA in patients with NSCLC were 88% (95% CI, 86–91), 72% (95% CI, 66–77), and 91% (95% CI, 89–93), respectively.
Conclusions: This large, multicenter, pragmatic study demonstrates that cytology samples obtained from EBUS-TBNA in routine practice are suitable for subtyping of NSCLC and EGFR mutation analysis and that the use of immunohistochemistry reduces the rate of NSCLC-NOS.
endobronchial ultrasound; non–small cell lung cancer; adenocarcinoma; EGFR mutation; NSCLC-NOS
The purpose of this study was to evaluate the usefulness of convex probe endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for detecting malignancy in parenchymal pulmonary lesions located adjacent to the central airways.
Materials and Methods
We retrospectively reviewed the diagnostic performance of EBUS-TBNA in consecutive patients with high clinical suspicion of a centrally located primary lung cancer who had undergone EBUS-TBNA at the Samsung Medical Center between May 2009 and June 2011.
Thirty-seven patients underwent EBUS-TBNA for intrapulmonary lesions adjacent to the central airways. Seven lesions were located adjacent to the trachea and 30 lesions were located adjacent to the bronchi. Cytologic and histologic samples obtained via EBUS-TBNA were diagnostic in 32 of 37 (86.4%) of patients. The final diagnosis was lung cancer in 30 patients (7 small cell lung cancer, 23 non-small cell lung cancer), lymphoma in one and malignant fibrous histiocytoma in one patient. The diagnostic sensitivity of EBUS-TBNA in detecting malignancy and detecting both malignancy and benignity was 91.4% and 86.5%, respectively. Two patients experienced minor complications.
EBUS-TBNA is an effective and safe method for tissue diagnosis of parenchymal lesions that lie centrally close to the airways. EBUS-TBNA should be considered the procedure of choice for patients with centrally located lesions without endobronchial involvement.
Bronchoscopy; endobronchial ultrasound; transbronchial needle aspiration; lung cancer; parenchymal lesion
There are no accurate data on the relationship between nodal station and diagnostic performance of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). We evaluated the impact of nodal station and size on the diagnostic performance of EBUS-TBNA in patients with non-small cell lung cancer (NSCLC). Consecutive patients who underwent EBUS-TBNA of mediastinal or hilar lymph nodes for staging or diagnosis of NSCLC were included in this retrospective study. Between May 2009 and February 2010, EBUS-TBNA was performed in 373 mediastinal and hilar lymph nodes in 151 patients. The overall diagnostic sensitivity, specificity, accuracy and negative predictive value (NPV) of EBUS-TBNA were 91.6%, 98.6%, 93.8%, and 84.3%, respectively. NPV of the left side nodal group was significantly lower than those of the other groups (P = 0.047) and sensitivity of the left side nodal group tended to decrease (P = 0.096) compared with those of the other groups. Diagnostic sensitivity and NPV of 4L lymph node were 83.3% and 66.7%, respectively. However, diagnostic performances of EBUS-TBNA did not differ according to nodal size. Bronchoscopists should consider the impact of nodal stations on diagnostic performances of EBUS-TBNA.
Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration; Lymph Nodes; Mediastinum; Non-Small Cell Lung Cancer
EGFR mutations correlate with improved clinical outcome whereas KRAS mutations are associated with lack of response to tyrosine kinase inhibitors in patients with non-small cell lung cancer (NSCLC). Endobronchial ultrasound (EBUS)-transbronchial needle aspiration (TBNA) is being increasingly used in the management of NSCLC. Co-amplification at lower denaturation temperature (COLD)–polymerase chain reaction (PCR) (COLD-PCR) is a sensitive assay for the detection of genetic mutations in solid tumours. This study assessed the feasibility of using COLD-PCR to screen for EGFR and KRAS mutations in cytology samples obtained by EBUS-TBNA in routine clinical practice. Samples obtained from NSCLC patients undergoing EBUS-TBNA were evaluated according to our standard clinical protocols. DNA extracted from these samples was subjected to COLD-PCR to amplify exons 18–21 of EGFR and exons two and three of KRAS followed by direct sequencing. Mutation analysis was performed in 131 of 132 (99.3%) NSCLC patients (70F/62M) with confirmed lymph node metastases (94/132 (71.2%) adenocarcinoma; 17/132 (12.8%) squamous cell; 2/132 (0.15%) large cell neuroendocrine; 1/132 (0.07%) large cell carcinoma; 18/132 (13.6%) NSCL-not otherwise specified (NOS)). Molecular analysis of all EGFR and KRAS target sequences was achieved in 126 of 132 (95.5%) and 130 of 132 (98.4%) of cases respectively. EGFR mutations were identified in 13 (10.5%) of fully evaluated cases (11 in adenocarcinoma and two in NSCLC-NOS) including two novel mutations. KRAS mutations were identified in 23 (17.5%) of fully analysed patient samples (18 adenocarcinoma and five NSCLC-NOS). We conclude that EBUS-TBNA of lymph nodes infiltrated by NSCLC can provide sufficient tumour material for EGFR and KRAS mutation analysis in most patients, and that COLD-PCR and sequencing is a robust screening assay for EGFR and KRAS mutation analysis in this clinical context.
Rationale: Patients with isolated mediastinal lymphadenopathy (IML) are a common presentation to physicians, and mediastinoscopy is traditionally considered the “gold standard” investigation when a pathological diagnosis is required. Endobronchial ultrasound–guided transbronchial needle aspiration (EBUS-TBNA) is established as an alternative to mediastinoscopy in patients with lung cancer.
Objective: To determine the efficacy and health care costs of EBUS-TBNA as an alternative initial investigation to mediastinoscopy in patients with isolated IML.
Methods: Prospective multicenter single-arm clinical trial of 77 consecutive patients with IML from 5 centers between April 2009 and March 2011. All patients underwent EBUS-TBNA. If EBUS-TBNA did not provide a diagnosis, then participants underwent mediastinoscopy.
Measurements and Main Results: EBUS-TBNA prevented 87% of mediastinoscopies (95% confidence interval [CI], 77–94%; P < 0.001) but failed to provide a diagnosis in 10 patients (13%), all of whom underwent mediastinoscopy. The sensitivity and negative predictive value of EBUS-TBNA in patients with IML were 92% (95% CI, 83–95%) and 40% (95% CI, 12–74%), respectively. One patient developed a lower respiratory tract infection after EBUS-TBNA, requiring inpatient admission. The cost of the EBUS-TBNA procedure per patient was £1,382 ($2,190). The mean cost of the EBUS-TBNA strategy was £1,892 ($2,998) per patient, whereas a strategy of mediastinoscopy alone was significantly more costly at £3,228 ($5,115) per patient (P < 0.001). The EBUS-TBNA strategy is less costly than mediastinoscopy if the cost per EBUS-TBNA procedure is less than £2,718 ($4,307) per patient.
Conclusions: EBUS-TBNA is a safe, highly sensitive, and cost-saving initial investigation in patients with IML.
Clinical trial registered with ClinicalTrials.gov (NCT00932854).
endobronchial ultrasound; mediastinal lymphadenopathy; sarcoidosis; tuberculosis; lymphoma
Since the development of endobronchial ultrasound-guided real-time needle aspiration (EBUS-rt-TBNA) no false positive (FP) cases have been described. We present the first FP case for EBUS-rt-TBNA secondary to a carcinoma in situ (CIS) in the bronchial point of puncture. A 66-years-old male was referred to our Institution because of a mass in left lower lobe. The bronchoscopy did not show any endobronchial lesion. The cytology of the washing confirmed an unspecified non-small cell lung cancer. An EBUS-rt-TBNA for staging was carried out. No mediastinal nodes over 5 mm length were found but one single left hilar node at station 11 L was sampled. The cytology of the TBNA showed lymphocytes and neoplastic squamous cells. The patient underwent thoracotomy. On the surgical specimen no metastasis on any of the nodes resected were detected but a CIS on the bronchial resection margin was described. A bronchial biopsy confirmed CIS on the bronchial stump. The reported case depicts an unusual situation, we consider EBUS-rt-TBNA an accurate technique if minimal requirements are met
Lung Cancer; Endobronchial Ultrasound; Staging; False Positive; Carcinoma in situ
Endobronchial Ultrasound Guided Transbronchial Needle Aspiration (EBUS-TBNA) and Trans-esophageal Ultrasound Scanning with Fine Needle Aspiration (EUS-FNA) are important, novel techniques for the diagnosis and staging of non-small cell lung cancer (NSCLC) that have been incorporated into lung cancer staging guidelines. To guide and optimize treatment decisions, especially for NSCLC patients in stage III and IV, EGFR and KRAS mutation status is often required. The concordance rate of the mutation analysis between these cytological aspirates and histological samples obtained by surgical staging is unknown. Therefore, we studied the extent to which allele-specific quantitative real-time PCR with hydrolysis probes could be reliably performed on EBUS and EUS fine needle aspirates by comparing the results with histological material from the same patient. We analyzed a series of 43 NSCLC patients for whom cytological and histological material was available. We demonstrated that these standard molecular techniques can be accurately applied on fine needle cytological aspirates from NSCLC patients. Importantly, we show that all mutations detected in the histological material of primary tumor were also identified in the cytological samples. We conclude that molecular profiling can be reliably performed on fine needle cytology aspirates from NSCLC patients.
Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has emerged as an important tool for the diagnosis and staging of lung cancer but its role in the diagnosis of tuberculous intrathoracic lymphadenopathy has not been established. The aim of this study was to describe the diagnostic utility of EBUS-TBNA in patients with intrathoracic lymphadenopathy due to tuberculosis (TB).
156 consecutive patients with isolated intrathoracic TB lymphadenitis were studied across four centres over a 2-year period. Only patients with a confirmed diagnosis or unequivocal clinical and radiological response to antituberculous treatment during follow-up for a minimum of 6 months were included. All patients underwent routine clinical assessment and a CT scan prior to EBUS-TBNA. Demographic data, HIV status, pathological findings and microbiological results were recorded.
EBUS-TBNA was diagnostic of TB in 146 patients (94%; 95% CI 88% to 97%). Pathological findings were consistent with TB in 134 patients (86%). Microbiological investigations yielded a positive culture of TB in 74 patients (47%) with a median time to positive culture of 16 days (range 3–84) and identified eight drug-resistant cases (5%). Ten patients (6%) did not have a specific diagnosis following EBUS; four underwent mediastinoscopy which confirmed the diagnosis of TB while six responded to empirical antituberculous therapy. There was one complication requiring an inpatient admission.
EBUS-TBNA is a safe and effective first-line investigation in patients with tuberculous intrathoracic lymphadenopathy.
Mediastinal lymphadenopathy in patients with an extrathoracic malignancy is a common clinical scenario. Invasive sampling of intrathoracic lymph nodes may be performed by mediastinoscopy or endoscopic ultrasound-guided fine needle aspiration. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is an alternative to mediastinoscopy and endoscopic ultrasound in patients with lung cancer and sarcoidosis. The utility of EBUS-TBNA in patients with extrathoracic malignancy was evaluated.
Consecutive patients who were suspected to have intrathoracic lymph node metastases from an extrathoracic malignancy underwent EBUS-TBNA. When EBUS-TBNA did not provide a specific diagnosis, patients underwent mediastinoscopy or clinical follow-up of at least 6 months duration.
One hundred sixty-one patients meeting the inclusion criteria underwent EBUS-TBNA in five UK centers over a 3-year period. EBUS-TBNA diagnosed mediastinal or hilar metastases in 71 (44%) patients, new lung cancer in 20 (12%) patients, and sarcoidosis in 14 (9%) patients. The sensitivity, negative predictive value for malignancy, and overall accuracy for EBUS-TBNA were 87%, 73% and 88%, respectively. One hundred ten (68%) patients in the study had a final diagnosis of malignant intrathoracic lymphadenopathy.
Because of the high prevalence of alternative diagnoses, pathological evaluation is important in patients with extrathoracic malignancy and suspected mediastinal or hilar lymph node metastases. EBUS-TBNA is a safe and sensitive technique and may be considered a first-line investigation in these patients.
Endobronchial ultrasound; Mediastinal lymphadenopathy; Breast cancer; Lung cancer
Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is an integral tool in the diagnosis and staging of malignant tumors of the lung. Rapid on-site evaluation (ROSE) of fine needle aspiration (FNA) samples has been advocated for as a guide for assessing the accuracy and adequacy of biopsy samples. Although ROSE has proven useful for numerous sites and procedures, few studies have specifically investigated its utility in the assessment of EBUS-TBNA specimens. The intention of this study was to explore the utility of ROSE for EBUS-TBNA specimens.
Materials and Methods:
The pathology files at our institution were searched for all EBUS-TBNA cases performed between January 2010 and June 2010. The data points included number of sites sampled per patient, location of site(s) sampled, on-site evaluation performed, preliminary on-site diagnosis rendered, final cytologic diagnosis, surgical pathology follow-up, cell blocks, and ancillary studies performed.
A total of 294 EBUS-TBNA specimens were reviewed and included in the study; 264 of 294 (90%) were lymph nodes and 30 of 294 (10%) were lung mass lesions. ROSE was performed for 140 of 294 (48%) specimens. The on-site and final diagnoses were concordant in 104 (74%) and discordant in 36 (26%) cases. Diagnostic specimens were obtained in 132 of 140 (94%) cases with on-site evaluation and 138 of 154 (90%) without on-site evaluation. The final cytologic diagnosis was malignant in 60 of 132 (45%) cases with ROSE and 46 of 138 (33%) cases without ROSE, and the final diagnosis was benign in 57 of 132 (47%) with ROSE and 82 of 138 (59%) without ROSE. A cell block was obtained in 129 of 140 (92%) cases with ROSE and 136 of 154 (88%) cases without ROSE.
The data demonstrate no remarkable difference in diagnostic yield, the number of sites sampled per patient, or clinical decision making between specimens collected via EBUS-TBNA with or without ROSE. As a result, this study challenges the notion that ROSE is beneficial for the evaluation of EBUS-TBNA specimens.
EBUS-TBNA; endobronchial; on-site; ROSE
Conventional smears of samples obtained by endobronchial ultrasound with real-time transbronchial needle aspiration (EBUS-TBNA) have proven useful in lung cancer staging, but the value of additional information from cell-block processing of EBUS-TBNA samples has only been marginally investigated. This study focussed on the contribution of cell block analysis to the diagnostic yield in lung cancer.
Patients referred for lung cancer diagnosis and/or staging by means of EBUS-TBNA were enrolled, the adequacy of the obtained samples for preparing cell blocks was assessed, and the additional pathologic or genetic information provided from cell block analysis was examined.
In 270 lung cancer patients referred for EBUS-TBNA (mean age, 63.3 SD 10.4 years) 697 aspirations were performed. Cell blocks could be obtained from 334 aspirates (47.9%) and contained diagnostic material in 262 (37.6%) aspirates, providing information that was additional to conventional smears in 50 of the 189 samples with smears that were non-diagnostic, corresponding 21 of these blocks to malignant nodes, and allowing lung cancer subtyping of 4 samples. Overall, cell blocks improved the pathologic diagnosis attained with conventional smears in 54 of the 697 samples obtained with EBUS-TBNA (7.7%). Cell blocks obtained during EBUS-TBNA also made epithelial growth factor receptor mutation analysis possible in 39 of the 64 patients with TBNA samples showing metastatic adenocarcinoma (60.1%). Overall, cell blocks provided clinically significant information for 83 of the 270 patients participating in the study (30.7%).
Cell-block preparation from EBUS-TBNA samples is a simple way to provide additional information in lung cancer diagnosis. Analysis of cell blocks increases the diagnostic yield of the procedure by nearly seven per cent and allows for genetic analysis in a sixty per cent of the patients with metastatic adenocarcinoma.
Cell block; Endobronchial ultrasound; Transbronchial needle aspiration; Lung cancer
With the recent widespread use of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), there have been occasional reports on complications associated with its use. Previous reviews on EBUS-TBNA have been limited to studies by skilled operators, thus the results may not always be applicable to recent clinical practice. To assess the safety of EBUS-TBNA for the staging and diagnosis of lung cancer in Japan, a nationwide survey on its current usage status and complications associated with its use was conducted by the Japan Society for Respiratory Endoscopy (JSRE).
A questionnaire about EBUS-TBNA performed between January 2011 and June 2012 was mailed to 520 JSRE-accredited facilities.
Responses were obtained from 455 facilities (87.5%). During the study period, EBUS-TBNA was performed in 7,345 cases in 210 facilities (46.2%) using a convex probe ultrasound bronchoscope, for 6,836 mediastinal and hilar lesions and 275 lung parenchymal lesions. Ninety complications occurred in 32 facilities. The complication rate was 1.23% (95% confidence interval, 0.97%-1.48%), with hemorrhage being the most frequent complication (50 cases, 0.68%). Infectious complications developed in 14 cases (0.19%) (Mediastinitis, 7; pneumonia, 4; pericarditis, 1; cyst infection, 1; and sepsis, 1). Pneumothorax developed in 2 cases (0.03%), one of which required tube drainage. Regarding the outcome of the cases with complications, prolonged hospitalization was observed in 14 cases, life-threatening conditions in 4, and death in 1 (severe cerebral infarction) (mortality rate, 0.01%). Breakage of the ultrasound bronchoscope occurred in 98 cases (1.33%) in 67 facilities (31.9%), and that of the puncture needle in 15 cases (0.20%) in 8 facilities (3.8%).
Although the complication rate associated with EBUS-TBNA was found to be low, severe complications, including infectious complications, were observed, and the incidence of device breakage was high. Since the use of EBUS-TBNA is rapidly expanding in Japan, an educational program for its safe performance should be immediately established.
Breakage; Bronchoscopic ultrasound; Bronchoscopy; Infection; Lung cancer; Mediastinitis; Mortality; Pulmonary intervention; Safety; Survey
Background and objective
Standard bronchoscopic techniques (transbronchial lung biopsy and endobronchial biopsy) provide a diagnosis in 70% of patients with pulmonary sarcoidosis. Previous data suggest that endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has a high sensitivity in patients with sarcoidosis. The feasibility and utility of combining EBUS-TBNA with standard bronchoscopic techniques is unknown. The aim of this study was to evaluate the feasibility, safety and efficacy of combined EBUS-TBNA and standard bronchoscopic techniques in patients with suspected sarcoidosis and enlarged mediastinal or hilar lymphadenopathy.
Forty consecutive patients with suspected pulmonary sarcoidosis and enlarged mediastinal or hilar lymph nodes (radiographical stage I and stage II) underwent EBUS-TBNA followed by transbronchial biopsies and endobronchial biopsies under conscious sedation.
Thirty-nine out of 40 patients successfully underwent combined EBUS-TBNA and standard bronchoscopy. Twenty-seven patients were diagnosed with sarcoidosis, eight had tuberculosis, two had reactive lymphadenopathy, two had lymphoma and one had metastatic adenocarcinoma. In patients with sarcoidosis, the sensitivity of EBUS-TBNA for detection of noncaseating granulomas was 85%, compared with a sensitivity of 35% for standard bronchoscopic techniques (P < 0.001). The diagnostic yield of combined EBUS-TBNA and bronchoscopy was 93% (P < 0.0001).
Combination of EBUS-TBNA with standard bronchoscopic techniques is safe and feasible, and optimizes the diagnostic yield in patients with pulmonary sarcoidosis and enlarged intrathoracic lymphadenopathy.
endobronchial ultrasound; mediastinal lymphadenopathy; sarcoidosis; transbronchial biopsy
We report a 54-year-old woman who presented with a well-defined, homogeneous, and non-enhancing mass in the retrobronchial region of the bronchus intermedius. The patient underwent endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for histological confirmation. Serous fluid was aspirated by EBUS-TBNA. Cytological examination identified an acellular smear with negative microbiological cultures. The patient was finally diagnosed with bronchogenic cysts by chest computed tomography (CT) and EBUS-TBNA findings. However, 1 week after EBUS-TBNA, the patient developed bronchogenic cyst rupture and pneumonia. Empirical antibiotics were administered, and pneumonia from the bronchogenic cyst rupture had resolved on follow-up chest CT. To our knowledge, this is the first reported case of pneumonia from bronchogenic cyst rupture after EBUS-TBNA.
Bronchogenic Cyst; Rupture; Pneumonia; Ultrasonography; Biopsy, Fine-Needle
Intrathoracic lymph node enlargement is a common finding in patients with extrathoracic malignancies. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a technique that is commonly used for lung cancer diagnosis and staging but that has not been widely investigated for the diagnosis of enlarged mediastinal and lobar lymph nodes in patients with extrathoracic malignancies. We conducted a retrospective study of 117 patients with extrathoracic malignancies who underwent EBUS-TBNA for diagnosis of intrathoracic lymph node enlargement from October 2005 to December 2009 and compared the EBUS-TBNA findings with the final diagnoses. EBUS-TBNA diagnosed mediastinal metastases in 51 of the 117 (43.6 %) cases and gave an alternate diagnosis or ruled out the presence of malignancy in 35 (56.4 %). Fourteen of these 35 patients underwent further surgical investigation, while the remaining 21 had clinical and radiological follow-up for 18 months. No false negatives were found in the surgery group. In the follow-up group, 13 patients had stable or regressive lymphadenopathy, and eight developed clinicoradiological progression and were assumed to have been false negatives by EBUS-TBNA. The sensitivity and negative predictive value of EBUS-TBNA were 86.4 and 75 %, respectively. Immunohistochemical staining (IHC) was performed in 80.4 % of the samples obtained by EBUS-TBNA. In samples obtained from ten patients with metastatic breast cancer, estrogen receptor expression was successfully assessed in eight patients and progesterone receptor and human epidermal growth factor receptor 2 in four. EBUS-TBNA is an accurate procedure for the diagnosis of thoracic lymph node metastases in patients with extrathoracic malignancies and should be an initial diagnostic tool in these patients. Furthermore, EBUS-TBNA can obtain high-quality specimens from metastatic lymph nodes for use in molecular analyses.
Endobronchial ultrasound; Transbronchial needle aspiration; EBUS-TBNA; Mediastinal lymph node metastases; Extrathoracic malignancy; Immunohistochemistry
In tuberculosis (TB)-endemic areas, contrast-enhanced computed tomography (CT) and positron emission tomography (PET) findings of lung cancer patients with non-enlarged lymph nodes are frequently discrepant. Endobronchial ultrasound-guided transbronchial aspiration (EBUS-TBNA) enables real-time nodal sampling, and thereby improves nodal diagnosis accuracy. This study aimed to compare the accuracy of nodal diagnosis by using EBUS-TBNA, and PET.
We studied 43 lung cancer patients with CT-defined non-enlarged mediastinal and hilar lymph nodes and examined 78 lymph nodes using EBUS-TBNA.
The sensitivity, specificity, positive predictive value, and negative predictive value of EBUS-TBNA were 80.6%, 100%, 100%, and 85.7%, respectively. PET had low specificity (18.9%) and a low positive predictive value (44.4%). The diagnostic accuracy of EBUS-TBNA was higher than that of PET (91% vs. 47.4%; p<0.001). Compared to CT-based nodal assessment, PET yielded a positive diagnostic impact in 36.9% nodes, a negative diagnostic impact in 46.2% nodes, and no diagnostic impact in 16.9% nodes. Patients with lymph nodes showing negative PET diagnostic impact had a high incidence of previous pulmonary TB. Multivariate analysis indicated that detection of hilar nodes on PET was an independent predictor of negative diagnostic impact of PET.
In a TB-endemic area with a condition of CT-defined non-enlarged lymph node, the negative diagnostic impact of PET limits its clinical usefulness for nodal staging; therefore, EBUS-TBNA, which facilitates direct diagnosis, is preferred.
Granulomatous inflammation has been previously reported in association with cancer. Endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) is a new minimally invasive test for investigating mediastinal lymphadenopathy. The identification of granulomatous inflammation by EBUS-TBNA and the clinical implications of such detection in a series of patients with previously treated cancer and new mediastinal lymphadenopathy has not previously been performed.
All 153 consecutive patients undergoing EBUS-TBNA in an academic cancer institution for suspected cancer in the mediastinum (mediastinal lymphadenopathy by CT imaging) were reviewed. Patients with non-caseating granuloma identified by EBUS-TBNA were included.
EBUS-TBNA identified non-caseating granuloma in 17/153 (11%) patients. A subset of 8/153 (5.2%) had sarcoid like lymphadenopathy mimicking cancer recurrence (5/5 PET positive). Another 8/153 (5.2%) patients with new mediastinal lymphadenopathy and no prior history of cancer had a clinical syndrome consistent with sarcoidosis. One other patient with a history of breast cancer was diagnosed with non-tuberculous mycobacteria infection. No patient required mediastinoscopy and there were no complications.
In an academic cancer institute, at least 5% of patients undergoing EBUS-TBNA have sarcoid-like lymphadenopathy mimicking cancer recurrence. Further studies to define the precise etiology, natural history and prognosis of this phenomenon are warranted.
Microscopic anthracotic pigment (MAP) is frequently observed in endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) specimen in non-small cell lung cancer, but its clinical interpretation is not well-known. The aim of this study was to evaluate the clinical implication of MAP in mediastinal staging of non-small cell lung cancer. From May 2010 to July 2011, consecutive potentially operable non-small cell lung cancer patients who underwent EBUS-TBNA for mediastinal staging were recruited. Of the total 133 patients, 102 (76.7%) were male patients. Median age was 68 yr. Total 279 mediastinal lymph nodes were sampled by EBUS-TBNA; station 4R (100, 35.8%) and station 7 (86, 30.8%) were the most common sites. Malignant lymph nodes were 100 (35.8%). MAP was observed in 61 (21.7%) lymph nodes, and among them only 3 were malignant lymph nodes (P < 0.001). The lymph nodes with MAP were smaller (9.0 vs 10.8 mm, P = 0.001) and showed low standard uptake values on FDG-PET (4.4 vs 4.7, P = 0.256). In multivariate analysis, MAP was negatively associated with malignant lymph node (adjusted OR, 0.12; 95% CI, 0.03-0.42; P < 0.001). In potentially operable non-small cell lung cancer patients, MAP in endobronchial ultrasound-guided transbronchial needle aspiration specimens is strongly associated with benign mediastinal and hilar lymph nodes.
Lung Cancer; Staging; Endobronchial Ultrasound; Anthracotic Pigment
Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has shown excellent diagnostic capabilities for mediastinal and hilar lymphadenopathy. However, its value in thoracic non-lymph node lesions is less clear. This study was designed to assess the value of EBUS-TBNA in distinguishing malignant from benign thoracic non-lymph node lesions.
From October 2009 to August 2011, 552 patients underwent EBUS-TBNA under local anesthesia and with conscious sedation. We retrospectively reviewed 81 of these patients who had tracheobronchial wall-adjacent intrapulmonary or isolated mediastinal non-lymph node lesions. On-site cytological evaluation was not used. Immunohistochemistry (IHC) was performed to distinguish the origin or type of malignancy when necessary.
EBUS-TBNA was performed in 68 tracheobronchial wall-adjacent intrapulmonary and 13 isolated mediastinal non-lymph node lesions. Of the 81 patients, 77 (95.1%, 60 malignancies and 17 benignancies) were diagnosed through EBUS-TBNA, including 57 primary lung cancers, 2 mediastinal tumors, 1 pulmonary metastatic adenocarcinoma, 7 inflammation, 5 tuberculosis, 3 mediastinal cysts, 1 esophageal schwannoma, and 1 focal fibrosis. There were four false-negative cases (4.9%). Of the 60 malignancies, there were 9 (15.0%) which originally had no definite histologic origin or type. Thus, IHC was performed, with 7 (77.8%) being subsequently confirmed. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of EBUS-TBNA in distinguishing malignant from benign lesions were 93.4% (60/64), 100% (17/17), 100% (60/60), 81.0% (17/21), and 95.1% (77/81), respectively.
EBUS-TBNA is a safe procedure with a high sensitivity for distinguishing malignant from benign thoracic non-lymph node lesions within the reach of EBUS-TBNA, with IHC usually providing a more definitive diagnosis.
Endobronchial ultrasound; immunohistochemistry; lung cancer; thoracic lesion; transbronchial needle aspiration
Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has been widely used for sampling of the mediastinum and hilar lesions for diagnosis or for staging of lung cancer. The viewing fields of EBUS Scope are 35 or 45 degrees forward oblique. This makes the manipulation of the scope very difficult. Plus its bigger external diameter, it is unusable for routine airway examination and biopsy. It is uncomfortable for the patient and often need general anesthesia and usually is preceded by a standard bronchoscopic examination. We tested a Fuji EBUS scope (EB-530 US) extensively on a bronchial cast and EBUS teaching phantom, then applied to the patient. This case report describes the unique quality of this EBUS scope and its potential. It has a 10 degrees forward oblique view and smaller external diameter. It might be able to eliminate the need of a second scope and makes the TBNA with or without EBUS simpler to do and easier to learn.
Endobronchial ultrasound-guided transbronchial needle aspiration; endobronchial ultrasound bronchoscope; sarcoidosis
Nodal staging of lung cancer is important for selecting surgical candidates. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) was evaluated as a modality for nodal staging of patients with potentially node-positive non-small cell lung cancer (NSCLC).
Endobronchial ultrasound-guided transbronchial needle aspiration was used for nodal staging of NSCLC patients with radiological N2/3 disease (short axis >10 mm on computed tomography and/or standardized positron emission uptake value >2.5 on 2-deoxy-2[F-18] fluoro-d-glucose positron emission tomography), T-stage ≥ T2, or positive serum carcinoembryonic antigen. Data on eligible patients were extracted from the database of our institution and analyzed for differences in nodal stages between radiological staging (RS) and EBUS-TBNA-integrated staging (ES), with validation by pathological staging of patients who had undergone surgery.
Of 480 eligible patients, there were 135 N0/1 and 345 N2/3 patients according to RS. Out of the 345 patients staged as N2/3 by RS, 113 (33 %) were downgraded to N0/1 by ES. Out of the 135 patients staged as N0/1 by RS, 12 (9 %) were upgraded to N2/3 by ES. Patients were restaged as N0/1 in 236 cases and N2/3 in 244 cases by ES, and the distributions of nodal stage between RS and ES were significantly different (p < 0.001). Finally, 215 out of the 236 ES-N0/1 patients underwent lung resection, and 195 (90.7 %) and 20 patients were staged by pathology as N0/1 and N2, respectively.
Endobronchial ultrasound-guided transbronchial needle aspiration is more accurate for lymph node staging compared to radiological staging. EBUS-TBNA can identify patients who are true candidates for surgery.
EBUS-TBNA; Staging; Lung cancer; FDG-PET; Lymph nodes
Transbronchial needle aspiration (TBNA) is an established method for sampling mediastinal lymph nodes to aid in diagnosing lymphadenopathy and in staging lung cancers. Real‐time endobronchial ultrasound (EBUS) guidance is a new method of TBNA that may increase the ability to sample these nodes and hence to determine a diagnosis. A descriptive study was conducted to test this new method.
Consecutive patients referred for TBNA of mediastinal lymph nodes were included in the trial. When a node was detected, a puncture was performed under real‐time ultrasound control. The primary end point was the number of successful biopsy specimens. Diagnostic results from the biopsies were compared with operative findings. Lymph node stations were classified according to the recently adopted American Thoracic Society scheme.
From 502 patients (316 men) of mean age 59 years (range 24–82), 572 lymph nodes were punctured and 535 (94%) resulted in a diagnosis. Biopsy specimens were taken from lymph nodes in region 2L (40 nodes), 2R (53 nodes), 3 (35 nodes), 4R (86 nodes), 4L (77 nodes), 7 (127 nodes), 10R (38 nodes), 10L (43 nodes), 11R (40 nodes) and 11L (33 nodes). The mean (SD) diameter of the nodes was 1.6 (0.36) cm and the range was 0.8–3.2 cm (SD range 0.8–4.3). Sensitivity was 94%, specificity 100%, and the positive predictive value was 100% calculated per patient. No complications occurred.
EBUS‐TBNA is a promising new method for sampling mediastinal lymph nodes. It appears to permit more and smaller nodes to be sampled than conventional TBNA, and it is safe.
lung cancer; transbronchial needle aspiration; endobronchial ultrasound; mediastinal lymphadenopathy
Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) biopsy is used to stage mediastinal lymph nodes in cancer patients to optimize treatment strategies. In this retrospective study, the authors determined the utility of EBUS-TBNA biopsy in the evaluation of mediastinal lymphadenopathy at a high-volume cancer center.
Materials and Methods:
The pathology database was searched for all patients who had undergone EBUS-TBNA biopsy of mediastinal lymph nodes over a one-year period. Cytologic diagnoses were correlated with clinical histories, subsequent resection, and clinical follow-up data.
Of 928 lymph node samples, 226 (24%) were diagnosed as malignant, 4 (0.4%) were suspicious for malignancy, 9 (1%) were atypical, 640 (69%) were benign, and 47 (5%) were insufficient for evaluation. In 89 (9.6%) cases, the patients had surgical resection. There was one false positive, in which the primary tumor contained infiltrating lymphocytes, had been sampled. There were five false-negative cases, which resulted from sampling errors, including two with micrometastases. The sensitivity, specificity, and positive and negative predictive value rates for EBUS-TBNA biopsy in the evaluation of mediastinal lymph nodes were 68.7% and 98.6% and 91.6% and 93.5%, respectively on a per lymph node basis. The overall clinical sensitivity, specificity, and positive and negative predictive value rates after one year clinical/radiological and histologic follow-up were 97%, 99.3%, 96.7% and 99.4%, respectively.
EBUS-TBNA biopsy is a sensitive and specific method for evaluating mediastinal lymphadenopathy in patients with lung and other primary tumors.
Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA); lymphadenopathy; lung cancer; lymph node metastasis; mediastinum; staging
The identification of mediastinal lymph nodes (LNs) in lung cancer is an important step of treatment decision and prognosis prediction. The endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is widely used to assess the mediastinal LNs and tissue confirmation in lung cancer. As use of bronchoscopy or EBUS-TBNA has been increased, bronchial anthracofibrosis (BAF) has been detected frequently. Moreover, BAF is often accompanied by mediastinal lymphadenopathy and showed false-positive positron emission tomography uptake, which mimics metastatic lymphadenopathy in lung cancer patients. However, clinical implication of BAF during bronchoscopy is not well understood in lung cancer. We retrospectively reviewed 536 lung cancer patients who performed EBUS-TBNA and observed BAF in 55 patients. A total of 790 LNs were analyzed and macroscopic tissue pigmentation was observed in 228 patients. The adjusted odds ratio for predicting malignant LN was 0.46 for BAF, and 0.22 for macroscopic tissue pigmentation. The specificity of BAF and macroscopic tissue pigmentation for predicting a malignant LN was 75.7% and 42.2%, respectively, which was higher than the specificity of using LN size or standard uptake value on PET. In conclusion, BAF and macroscopic tissue pigmentation during EBUS-TBNA are less commonly found in malignant LNs than reactive LNs in Korean lung cancer patients.
Anthracofibrosis; Malignant Lymph Node; Lung Neoplasms; EBUS-TBNA
Diagnosis of mediastinal/hilar lymph nodes and tumours is often challenging for patients with previously treated thoracic malignancy, especially when they have a history of thoracotomy. Endobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA) has been proposed as a safe, less-invasive modality for such patients. We retrospectively evaluated the role of EBUS-TBNA in the assessment of newly developed mediastinal/hilar abnormalities in patients with previously treated thoracic malignancy. Of 79 patients who underwent EBUS-TBNA between July 2009 and July 2011, 14 patients (18%) had a history of treatment for thoracic malignancy. In all patients, malignancy was confirmed again for the newly developed mediastinal/hilar abnormalities and three of them (21%) presented with a different pathology from the previous malignancy. Out of 14 patients, 12 had a history of thoracotomy and EBUS-TBNA was a useful, less-invasive diagnostic method particularly for these patients. Out of 14 patients, 11 (79%) had a history of lung cancer and 10 of them (91%) had received surgical resection. In conclusion, we confirmed that EBUS-TBNA obtained the pathological diagnosis in a less-invasive manner in all cases. Despite the small number of cases, our results can reveal the usefulness of EBUS-TBNA particularly in patients with previously treated thoracic malignancy.
Endobronchial ultrasound; Endobronchial ultrasound-guided transbronchial needle aspiration; Lung cancer; Malignancy; Recurrence