The diagnostic utility of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in lung cancer diagnosis and staging, including biomarker analysis, is currently widely recognized.1–3 In addition, EBUS-TBNA is used not only in lung cancer diagnosis and staging but also in the diagnosis of lymphoma and solid non-lung malignancies. This broader use of EBUS-TBNA results from the growing interest in using less invasive endoscopic techniques with lower complication rates.4
At this time, data on the diagnostic accuracy of EBUS-TBNA for lymphoma are still questionable. Surgical excision and core biopsy remain the preferred sampling techniques for lymphoma, because disease management often pivots on the pathologic subtype and grade, and there is this concern that the smaller samples obtained via EBUS-TBNA may not be sufficient to guide treatment decisions.5 Therefore, many clinicians still advocate that EBUS-TBNA is not a suitable diagnostic tool for lymphoma.
However, developing data suggest that, when EBUS is used along with appropriate immunohistochemical, flow cytometric, cytogenetic, and molecular studies, it can definitively diagnose lymphoma.5–7 In a recent study of patients who underwent EBUS-TBNA for suspected lymphoma, of the 75 patients who were ultimately established as having lymphoma, EBUS-TBNA was diagnostic in 63 (84%).5 In association with flow cytometry and immunohistochemical analysis, EBUS-TBNA had an overall sensitivity of 77%, specificity of 100%, and negative predictive value of 86% in the diagnosis and subtyping of de novo and recurrent lymphoma.5 Nevertheless, EBUS-TBNA performed differently for different types of lymphoma. EBUS-TBNA performed best among patients with a final diagnosis of low-grade non-Hodgkin lymphoma, with a 92% sensitivity rate.5 EBUS-TBNA did not perform as well at diagnosing Hodgkin lymphoma, likely due to failure to find characteristic Reed-Stenberg cells.5,8 On-site assessment likely improved diagnostic yield in these cases, as all the samples were screened for adequacy and appropriately assigned to ancillary testing.5
In an article published online in October 2017 in Journal of Bronchology and Interventional Pulmonology, Gandotra et al9 present their experience with EBUS-TBNA for the diagnosis of lymphoma. In this retrospective study, the authors reviewed the records of 806 patients who underwent EBUS-TBNA at their institution and found 20 patients with the final diagnosis of lymphoma.9 Of the 20 patients, 9 were diagnosed with de novo lymphoma and 11 were diagnosed with recurrent lymphoma.9 EBUS-TBNA established the diagnosis of de novo lymphoma in 7 (78%) of the 9 patients (78%) and recurrent lymphoma in 10 (91%) of the 11patients.9 All 3 cases that failed to be diagnosed by EBUS-TBNA had atypical cells on cytopathology; however, further characterization of the atypical cells was lacking either due to inadequate cell block material or nonspecific phenotype by flow cytometry.9
What were the main findings of the study? The authors found once again that EBUS-TBNA is an effective first diagnostic test in patients with suspected lymphoma.
The study by Gandotra and colleagues had a few limitations, including a retrospective design rather than a randomized trial or a study of multicenter registries and a very small sample size. Also, as the authors point out, the generalizability of the results depends on the amount of pathology resources available—in this case the use of on-site assessment with cytopathology support and screening for cellularity and adequacy for ancillary tests, including flow cytometry. All the patients in this study had 2 to 4 dedicated needle passes obtained for flow cytometry.9
Similar to the report by Gandotra and colleagues, others studies have shown that samples obtained by EBUS-TBNA can be adequate for lymphoma diagnosis. For instance, a review of patients referred for EBUS-TBNA between August 2005 and December 2006 at our institution in which EBUS-TBNA identified lymphoma in 10 (90.9%) of 11 patients.5,10 The findings in this study were similar to the sensitivity of 89% reported by Moonim et al8 in one of the largest such studies to date, with 100 lymphoma cases. Likewise, in a report by Senturk et al,11 the sensitivity of EBUS-TBNA for the diagnosis of lymphoma was calculated as 86.7%. The above findings are in contrast with those reported by Iqbal et al,12 who found an overall diagnostic sensitivity for lymphoma of only 29%.
So what’s different? One of the main differences between studies reporting high sensitivity and low sensitivity for EBUS-TBNA in lymphoma diagnosis is the use of on-site assessment with triage of available material. The theory behind this is that triaging material at the time of the procedure ensures that adequate material is available for cytologic or ancillary studies, especially for immunophenotyping at the time of biopsy. Triaging allows us to make procedural decisions, such as increasing the number of passes to maximize the yield. Therefore, immediate on-site assessment is necessary for an appropriate diagnostic workup of lymphoproliferative disorders in patients with mediastinal lymphadenopathy.7,13
In summary, with recent advances in diagnostic approach, such as the use of on-site assessment and flow cytometry, EBUS-TBNA is effective for diagnosing lymphoma and should be considered as a first diagnostic step in patents with suspected lymphoma with isolated mediastinal lymphadenopathy. In addition, EBUS-TBNA can provide sufficient information for subtyping in most cases. Moreover, with the availability of the novel 19-G flexible EBUS needle, we may see better diagnostic yields, but this needs to be explored in further studies.14
1. Jurado J, Saqi A, Maxfield R, et al. The efficacy of EBUS-guided transbronchial needle aspiration for molecular testing in lung adenocarcinoma. Ann Thorac Surg. 2013;96:1196–1202.
2. Schmid-Bindert G, Wang Y, Jiang H, et al. EBUS-TBNA provides highest RNA yield for multiple biomarker testing from routinely obtained small biopsies in non-small cell lung cancer patients—a comparative study of three different minimal invasive sampling methods. PLoS One. 2013;8:e77948.
3. Wahidi MM, Herth F, Yasufuku K, et al. Technical aspects of endobronchial ultrasound-guided transbronchial needle aspiration: CHEST Guideline and Expert Panel Report. Chest. 2016;149:816–835.
4. Ernst A, Anantham D, Eberhardt R, et al. Diagnosis of mediastinal adenopathy-real-time endobronchial ultrasound guided needle aspiration versus mediastinoscopy. J Thorac Oncol. 2008;3:577–582.
5. Grosu HB, Iliesiu M, Caraway NP, et al. Endobronchial ultrasound-guided transbronchial needle aspiration for the diagnosis and subtyping of lymphoma. Ann Am Thorac Soc. 2015;12:1336–1344.
6. Soldini D, Campo E. New insights into the diagnosis of lymphomas. Ann Oncol. 2012;23:x83–x88.
7. Ko HM, da Cunha Santos G, Darling G, et al. Diagnosis and subclassification of lymphomas and non-neoplastic lesions involving mediastinal lymph nodes using endobronchial ultrasound-guided transbronchial needle aspiration. Diagn Cytopathol. 2013;41:1023–1030.
8. Moonim MT, Breen R, Fields PA, et al. Diagnosis and subtyping of de novo and relapsed mediastinal lymphomas by endobronchial ultrasound needle aspiration. Am J Respir Crit Care Med. 2013;188:1216–1223.
9. Gandotra S, Dotson T, Lamar Z, et al. Endobronchial ultrasound transbronchial needle aspiration for the diagnosis of lymphoma. J Bronchol Interv Pulmonol. 2018;25:97–102.
10. Kennedy MP, Jimenez CA, Bruzzi JF, et al. Endobronchial ultrasound-guided transbronchial needle aspiration in the diagnosis of lymphoma. Thorax. 2008;63:360–365.
11. Senturk A, Babaoglu E, Kilic H, et al. Endobronchial ultrasound-guided transbronchial needle aspiration in the diagnosis of lymphoma. Asian Pac J Cancer Prev. 2014;15:4169–4173.
12. Iqbal S, DePew ZS, Kurtin PJ, et al. Endobronchial ultrasound and lymphoproliferative disorders: a retrospective study. Ann Thorac Surg. 2012;94:1830–1834.
13. Marshall CB, Jacob B, Patel S, et al. The utility of endobronchial ultrasound-guided transbronchial needle aspiration biopsy in the diagnosis of mediastinal lymphoproliferative disorders. Cancer Cytopathol. 2011;119:118–126.
14. Tyan C, Patel P, Czarnecka K, et al. Flexible 19-gauge endobronchial ultrasound-guided transbronchial needle aspiration needle: first experience. Respiration. 2017;94:52–57.