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David E. Ost, MD, MPH, FCCP
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From the Department of Pulmonary Medicine, University of Texas MD Anderson Cancer Center.

Correspondence to: David E. Ost, MD, MPH, FCCP, Department of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1462, Houston, TX 77030; e-mail: dost@mdanderson.org


Financial/nonfinancial disclosures: The author has reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2012;142(5):1356-1357. doi:10.1378/chest.12-2024
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To the Editor:

I thank Dr Dieter for his interest in our article1 on endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and for this interesting case report. Our study was a report on the clinical effectiveness and determinants of diagnostic yield. For most patients, surgical confirmation of positive EBUS-TBNA cytology results is not warranted as part of the standard of care, so patients did not undergo routine surgical confirmation in our study when EBUS-TBNA results were positive. Thus, the false-positive rate cannot be determined. This was a necessary trade-off, since it would be impractical to obtain surgical biopsies on all cases in everyday practice.

There is, however, a good body of literature demonstrating that although false-positive EBUS-TBNA cases occur, they are very rare.2-5 Two separate meta-analyses reported a pooled specificity for EBUS-TBNA of 100%.2,3 In the meta-analysis by Adams et al,3 one case of a false-positive result was identified.6 However, it is important to note that some of the studies used in these meta-analyses did not include surgery as a reference standard when positive EBUS-TBNA results were available, so positive EBUS-TBNA results were by definition “true positive” in those studies. A more recent retrospective review found a specificity of 98.6% (95% CI, 92.4%-99.8%).5 A prospective observational study of 153 patients in which all patients had completed both EBUS-TBNA and mediastinoscopy, using thoracotomy as the reference standard, found that both EBUS-TBNA and mediastinoscopy had 100% specificity. As a consequence, positive EBUS-TBNA results should be viewed as sufficient evidence of nodal disease to guide treatment decisions in most patients.

The case reported by Dr Dieter highlights one potential cause of false-positive results—specifically, passing the EBUS-TBNA needle through the node and into an adjacent parenchymal lung tumor. The case description says that both right hilar and right paratracheal lymph nodes demonstrated malignant cells, but the lymph node stations are not specified. Similarly, it says there was a right-sided tumor, but the lobe is not specified, so it is difficult to draw conclusions. It seems most likely, based on the information provided, that the EBUS-TBNA positive lymph nodes were the 10R or 11R and the 4R, and the tumor was in the right upper lobe. If the tumor was in the right upper lobe, adjacent to the trachea, and extended into the area of the right mainstem bronchus and right upper lobe take-off, it is plausible that both 11R and 4R EBUS-TBNA samples could be falsely positive. Alternatively, it might have been only the 4R that was false positive, since the 11R would not have changed the decision on surgery. It is difficult to tell from the description provided. It would be useful to clarify what the findings were that led Dr Dieter and his team to identify the nodes as negative and to recommend surgery. Since review of the prior biopsy showed both lymph nodes and cancer, presumably it was the prior CT scan and PET scan images rather than the cytology results that provided this information. Tumor adjacent to but not directly invading the 4R and/or 10R or 11R lymph nodes might have been identified by CT/PET scan. Additional images would be useful to clarify this. If there was direct extension of the tumor into the 4R region, this would provide supporting evidence that this was indeed a false-positive result.

On balance, it is important to recognize that false-positive results do occur with EBUS-TBNA, but they are very rare. Proper technique is important to limit the number of false positive results. As Dr Dieter’s case points out, passing the EBUS-TBNA needle through a benign node into adjacent parenchymal tumor is one possible cause of false-positive results. Other causes include contamination from other lymph nodes or endobronchial disease. To limit the number of false-positive results when performing EBUS-TBNA, physicians should sample the highest lymph node stations first (ie, sample N3 nodes first, then N2, then N1) so as to avoid contamination of the needle with malignant cells. Similarly, any areas of endobronchial disease should only be biopsied after all necessary lymph node stations have been sampled. Finally, it is important to control the depth of needle penetration to ensure that the distance traversed is completely within the lymph node. Obtaining a clear posterior border of the lymph node on ultrasound is very important in this regard, as Dr Dieter’s case highlights, since it is possible to pass through a benign lymph node and into an adjacent area of tumor. This in turn can lead to false-positive results with resultant accidental upstaging.

Ost DE, Ernst A, Lei X, et al; AQuIRE Bronchoscopy Registry Diagnostic yield of endobronchial ultrasound-guided transbronchial needle aspiration: results of the AQuIRE Bronchoscopy Registry. Chest. 2011;140(6):1557-1566. [CrossRef] [PubMed]
 
Gu P, Zhao YZ, Jiang LY, Zhang W, Xin Y, Han BH. Endobronchial ultrasound-guided transbronchial needle aspiration for staging of lung cancer: a systematic review and meta-analysis. Eur J Cancer. 2009;45(8):1389-1396. [CrossRef] [PubMed]
 
Adams K, Shah PL, Edmonds L, Lim E. Test performance of endobronchial ultrasound and transbronchial needle aspiration biopsy for mediastinal staging in patients with lung cancer: systematic review and meta-analysis. Thorax. 2009;64(9):757-762. [CrossRef] [PubMed]
 
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(6):1393-1400. [CrossRef] [PubMed]
 
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(1):46-51. [CrossRef] [PubMed]
 
Okamoto H, Watanabe K, Nagatomo A, et al. Endobronchial ultrasonography for mediastinal and hilar lymph node metastases of lung cancer. Chest. 2002;121(5):1498-1506. [CrossRef] [PubMed]
 

Figures

Tables

References

Ost DE, Ernst A, Lei X, et al; AQuIRE Bronchoscopy Registry Diagnostic yield of endobronchial ultrasound-guided transbronchial needle aspiration: results of the AQuIRE Bronchoscopy Registry. Chest. 2011;140(6):1557-1566. [CrossRef] [PubMed]
 
Gu P, Zhao YZ, Jiang LY, Zhang W, Xin Y, Han BH. Endobronchial ultrasound-guided transbronchial needle aspiration for staging of lung cancer: a systematic review and meta-analysis. Eur J Cancer. 2009;45(8):1389-1396. [CrossRef] [PubMed]
 
Adams K, Shah PL, Edmonds L, Lim E. Test performance of endobronchial ultrasound and transbronchial needle aspiration biopsy for mediastinal staging in patients with lung cancer: systematic review and meta-analysis. Thorax. 2009;64(9):757-762. [CrossRef] [PubMed]
 
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(6):1393-1400. [CrossRef] [PubMed]
 
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(1):46-51. [CrossRef] [PubMed]
 
Okamoto H, Watanabe K, Nagatomo A, et al. Endobronchial ultrasonography for mediastinal and hilar lymph node metastases of lung cancer. Chest. 2002;121(5):1498-1506. [CrossRef] [PubMed]
 
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