1164
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
5. Vroegop AV, Vanderveken OM, Dieltjens M, Wouters K, Saldien V, Braem MJ, Van de Heyning PH. Sleep endoscopy with simulation bite for prediction of oral appliance treatment outcome. J Sleep Res 2013; 22:348–355. Copyright ª 2013 by the American Thoracic Society
Importance of Onsite Cytopathology at Endobronchial Ultrasound To the Editor:
We read with interest the article by Navani and colleagues (1), which demonstrates well that samples obtained by endobronchial ultrasound-guided transbronchial needle aspiration (EBUSTBNA) can be used to subtype and genotype non–small cell lung cancer (NSCLC). However, we are keen to point out that their techniques used to obtain the sample may not necessarily be delivering the best yields for further investigations. In contrast to the authors, we use rapid onsite evaluation by a cytopathologist (ROSE) to help triage samples, which is effective both for tuberculosis (TB) molecular diagnostics and culture and for optimal cancer immunophenotyping and molecular diagnostics. In their study, 241 patients with either “lymphoid cells only” or insufficient sample seen in the cell block (i.e., a nondiagnostic aspirate) were thought not to have cancer by EBUS-TBNA. Of these, 69 (w1 in 3) went on to have a diagnosis of cancer within 6 months. In this “nondiagnostic” group, we believe ROSE should play a pivotal role. ROSE enables continued sampling of the nodes until a diagnosis is achieved on a direct smear. Further sampling is then possible to ensure adequate material for immunocytochemistry (ICC), and genotyping is taken. In contrast, in the current study there was no bedside analysis, and only one section of the cell block was examined. Of the lung cancer cases in this study, 23% (101 of 434) had a final diagnosis of NSCLC-not otherwise specified (NOS). Of this group, only 52% had ICC performed. Given that ICC is the one variable identified in this study that predicts the category NSCLC-NOS, all samples ideally should have ICC. In our institution, all EBUSTBNA samples diagnosed as NSCLC would generally go on to have ICC, and if adenocarcinoma is seen on morphological stains, then epidermal growth factor receptor analysis is requested. The samples we obtain using ROSE are bedside smeared and stained with DiffQuick and then the liquid needle washing samples are cytospun for the ICC slides and the remainder prepared as a cell block. Using ROSE in our center, of 352 patients undergoing an EBUS procedure, 102 patients were suspected of having NSCLC (unpublished data). Of these, 28 did not have a diagnosis of malignancy on EBUS. Three of these patients were referrals from peripheral hospitals and were lost to follow-up; three patients had a diagnosis of NSCLC by bronchial biopsy or transbronchial biopsy in the same procedure as EBUS; 20 were true negatives with an alternative diagnosis; and two patients went on to have malignancy over a 6-month period. Overall this gives a false-negative rate of 9.1%. Of our 74 patients with malignant cells diagnosed at EBUS, 24 were given a label of NSCLC-NOS on Diff-Quik staining at the bedside. However, the final diagnosis of NSCLC-NOS was only given in two patients or 3% of the 61 malignant cases that were lung cancers. Nineteen of the 24 NSCLC-NOS cases had ICC, which in one case did not help define the cancer beyond NSCLC-NOS. Three patients had a specific diagnosis of a nonlung primary after ICC. Of the five cases that did not have ICC, one patient had ICC performed on cells from a bronchoalveolar lavage performed at the time; two patients had a morphological diagnosis * Joint first authors.
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of squamous cell carcinoma, which was made on Giemsa staining of the direct preparations and Papanicolaou staining of the needle washings, both of which give more detail than Diff-Quik staining; and two patients were left with a diagnosis of NSCLC-NOS. Rossi emphasized the role of the pathologist in optimizing the use of tumor material for diagnostic purposes and ideally leaving remaining tissue for research (2). We argue that this role should begin at the bedside. First, the pathologist can ensure that the amount of tissue sampled is maximized by directing the endoscopist to resample the most successful target. Second, the bedside diagnosis prevents material being sent for inappropriate auxiliary investigations such as TB polymerase chain reaction and culture. Furthermore, only 197 of 1047 nodes sampled were from stations 10 and 11 in this study, with the majority being from stations 7 and 4R, where the average node size was large (.2 cm), and therefore less likely to benefit from ROSE as these stations and node sizes are more accessible. The node stations less frequently sampled were smaller and less well-represented in this study but are likely to benefit more from ROSE. Further studies are needed to compare the adequacy of sampling and triaging for diagnostics with and without ROSE, before deciding on specific methodologies. Therefore, at this stage, centers using ROSE should audit their own practice before deciding that no ROSE is required. Author disclosures are available with the text of this letter at www.atsjournals.org.
Clare Elizabeth Honor Craig, B.M.B.Ch.* Melissa Wickremasinghe, M.B.B.S., Ph.D.* Lydia Finney, M.B.B.Ch., B.Sc. Corrina B. Wright, M.B.B.Ch.B.A.O. Matthew Berry, M.B.B.Chir., Ph.D. Onn Min Kon, M.B.B.S., M.D. Imperial College Healthcare NHS Trust London, United Kingdom References 1. Navani N, Brown JM, Nankivell M, Woolhouse I, Harrison RN, Vandana J, Munavvar M, Ng BN, Rassl DM, Falzon M, et al. Suitability of endobronchial ultrasound-guided transbronchial needle aspiration specimens for subtyping and genotyping of non–small cell lung cancer: a multicenter study of 774 patients. Am J Respir Crit Care Med 2012;185:1316–1322. 2. Rossi G. Wanted: lung cancer pathologists. Am J Respir Crit Care Med 2013;187:450. Copyright ª 2013 by the American Thoracic Society
Reply: Optimum Performance of Endobronchial Ultrasound-guided Transbronchial Needle Aspiration From the Authors:
We thank Dr. Craig and colleagues for their interest in our article on the utility of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) specimens for the phenotyping and genotyping of non–small cell lung cancer (1). Dr. Craig and colleagues raise the issue of the value of rapid onsite evaluation (ROSE) by a cytopathologist and suggest that the techniques used in our article may not be yielding the best results for our patients. We disagree. Dr. Craig and colleagues overstate clinical conclusions based on a single-center retrospective uncontrolled series and choose to omit available published data from randomized controlled trials of ROSE. Furthermore, their assertion that ROSE may be superior to no ROSE is not supported by the selected data they present. The
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
5. Vroegop AV, Vanderveken OM, Dieltjens M, Wouters K, Saldien V, Braem MJ, Van de Heyning PH. Sleep endoscopy with simulation bite for prediction of oral appliance treatment outcome. J Sleep Res 2013; 22:348–355. Copyright ª 2013 by the American Thoracic Society
Importance of Onsite Cytopathology at Endobronchial Ultrasound To the Editor:
We read with interest the article by Navani and colleagues (1), which demonstrates well that samples obtained by endobronchial ultrasound-guided transbronchial needle aspiration (EBUSTBNA) can be used to subtype and genotype non–small cell lung cancer (NSCLC). However, we are keen to point out that their techniques used to obtain the sample may not necessarily be delivering the best yields for further investigations. In contrast to the authors, we use rapid onsite evaluation by a cytopathologist (ROSE) to help triage samples, which is effective both for tuberculosis (TB) molecular diagnostics and culture and for optimal cancer immunophenotyping and molecular diagnostics. In their study, 241 patients with either “lymphoid cells only” or insufficient sample seen in the cell block (i.e., a nondiagnostic aspirate) were thought not to have cancer by EBUS-TBNA. Of these, 69 (w1 in 3) went on to have a diagnosis of cancer within 6 months. In this “nondiagnostic” group, we believe ROSE should play a pivotal role. ROSE enables continued sampling of the nodes until a diagnosis is achieved on a direct smear. Further sampling is then possible to ensure adequate material for immunocytochemistry (ICC), and genotyping is taken. In contrast, in the current study there was no bedside analysis, and only one section of the cell block was examined. Of the lung cancer cases in this study, 23% (101 of 434) had a final diagnosis of NSCLC-not otherwise specified (NOS). Of this group, only 52% had ICC performed. Given that ICC is the one variable identified in this study that predicts the category NSCLC-NOS, all samples ideally should have ICC. In our institution, all EBUSTBNA samples diagnosed as NSCLC would generally go on to have ICC, and if adenocarcinoma is seen on morphological stains, then epidermal growth factor receptor analysis is requested. The samples we obtain using ROSE are bedside smeared and stained with DiffQuick and then the liquid needle washing samples are cytospun for the ICC slides and the remainder prepared as a cell block. Using ROSE in our center, of 352 patients undergoing an EBUS procedure, 102 patients were suspected of having NSCLC (unpublished data). Of these, 28 did not have a diagnosis of malignancy on EBUS. Three of these patients were referrals from peripheral hospitals and were lost to follow-up; three patients had a diagnosis of NSCLC by bronchial biopsy or transbronchial biopsy in the same procedure as EBUS; 20 were true negatives with an alternative diagnosis; and two patients went on to have malignancy over a 6-month period. Overall this gives a false-negative rate of 9.1%. Of our 74 patients with malignant cells diagnosed at EBUS, 24 were given a label of NSCLC-NOS on Diff-Quik staining at the bedside. However, the final diagnosis of NSCLC-NOS was only given in two patients or 3% of the 61 malignant cases that were lung cancers. Nineteen of the 24 NSCLC-NOS cases had ICC, which in one case did not help define the cancer beyond NSCLC-NOS. Three patients had a specific diagnosis of a nonlung primary after ICC. Of the five cases that did not have ICC, one patient had ICC performed on cells from a bronchoalveolar lavage performed at the time; two patients had a morphological diagnosis * Joint first authors.
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of squamous cell carcinoma, which was made on Giemsa staining of the direct preparations and Papanicolaou staining of the needle washings, both of which give more detail than Diff-Quik staining; and two patients were left with a diagnosis of NSCLC-NOS. Rossi emphasized the role of the pathologist in optimizing the use of tumor material for diagnostic purposes and ideally leaving remaining tissue for research (2). We argue that this role should begin at the bedside. First, the pathologist can ensure that the amount of tissue sampled is maximized by directing the endoscopist to resample the most successful target. Second, the bedside diagnosis prevents material being sent for inappropriate auxiliary investigations such as TB polymerase chain reaction and culture. Furthermore, only 197 of 1047 nodes sampled were from stations 10 and 11 in this study, with the majority being from stations 7 and 4R, where the average node size was large (.2 cm), and therefore less likely to benefit from ROSE as these stations and node sizes are more accessible. The node stations less frequently sampled were smaller and less well-represented in this study but are likely to benefit more from ROSE. Further studies are needed to compare the adequacy of sampling and triaging for diagnostics with and without ROSE, before deciding on specific methodologies. Therefore, at this stage, centers using ROSE should audit their own practice before deciding that no ROSE is required. Author disclosures are available with the text of this letter at www.atsjournals.org.
Clare Elizabeth Honor Craig, B.M.B.Ch.* Melissa Wickremasinghe, M.B.B.S., Ph.D.* Lydia Finney, M.B.B.Ch., B.Sc. Corrina B. Wright, M.B.B.Ch.B.A.O. Matthew Berry, M.B.B.Chir., Ph.D. Onn Min Kon, M.B.B.S., M.D. Imperial College Healthcare NHS Trust London, United Kingdom References 1. Navani N, Brown JM, Nankivell M, Woolhouse I, Harrison RN, Vandana J, Munavvar M, Ng BN, Rassl DM, Falzon M, et al. Suitability of endobronchial ultrasound-guided transbronchial needle aspiration specimens for subtyping and genotyping of non–small cell lung cancer: a multicenter study of 774 patients. Am J Respir Crit Care Med 2012;185:1316–1322. 2. Rossi G. Wanted: lung cancer pathologists. Am J Respir Crit Care Med 2013;187:450. Copyright ª 2013 by the American Thoracic Society
Reply: Optimum Performance of Endobronchial Ultrasound-guided Transbronchial Needle Aspiration From the Authors:
We thank Dr. Craig and colleagues for their interest in our article on the utility of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) specimens for the phenotyping and genotyping of non–small cell lung cancer (1). Dr. Craig and colleagues raise the issue of the value of rapid onsite evaluation (ROSE) by a cytopathologist and suggest that the techniques used in our article may not be yielding the best results for our patients. We disagree. Dr. Craig and colleagues overstate clinical conclusions based on a single-center retrospective uncontrolled series and choose to omit available published data from randomized controlled trials of ROSE. Furthermore, their assertion that ROSE may be superior to no ROSE is not supported by the selected data they present. The
