Does needle size affect the diagnostic yield of endobronchial ultrasound-guided transbronchial needle aspiration for malignant lymphoma?—a narrative review
Introduction
Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a widely performed, valuable technique for diagnosing not only malignant tumors such as lung cancer, metastatic cancer, and malignant lymphoma, as well as benign diseases, such as sarcoidosis. EBUS-TBNA is recommended for the diagnosis of malignant lymphoma; however, the amount of tissue obtained is often small, and previously reported diagnostic yields vary widely, from approximately 50% to 90% (1-6). Despite differences in whether studies included subtype determination, the diagnostic challenge of malignant lymphoma remains well recognized. In recent decades, the use of larger-diameter needles, such as 21-gauge (21G) and 19-gauge (19G) has become possible, which theoretically allows the collection of larger tissue samples (7). Notably, several studies have reported the efficacy of 19G, particularly for diagnosing sarcoidosis (8). Therefore, larger needles seem to improve the diagnostic yield; however, for malignant tumors, including lymphoma, the diagnostic advantage of 19G remains controversial (9-13). Therefore, in this review, we aimed to summarize current evidence regarding the diagnostic yield of EBUS-TBNA for malignant lymphoma and evaluated the usefulness of different needle devices. We present this article in accordance with the Narrative Review reporting checklist (available at https://med.amegroups.com/article/view/10.21037/med-2025-1-53/rc).
Methods
A comprehensive and systematic online literature search of PubMed was conducted using the keywords (“malignant lymphoma” OR “lymphoma”) AND (“endobronchial ultrasound” OR “endobronchial ultrasound guided” OR “endobronchial ultrasound guided transbronchial needle aspiration” OR “EBUS” OR “EBUS-TBNA” OR “needle size”). The search included studies published up to July 2025, and filters were used for “Humans”, “English”, and “Full text”. We selected only studies that enrolled adult patients and excluded reports involving fewer than ten patients with malignant lymphoma to reduce the potential bias associated with small sample sizes. When summarizing eligible articles, we defined “diagnostic yield” as “the proportion of cases in which the subtype of malignant lymphoma was successfully determined”. Studies without a description of lymphoma subtype were excluded from the analysis. Ultimately, 14 articles met the inclusion criteria and were analyzed (Figure 1). The search strategy is presented in Table 1.
Table 1
| Items | Specification |
|---|---|
| Date of search | August 1, 2025 |
| Database searched | PubMed |
| Search terms used | (“malignant lymphoma” OR “lymphoma”) and (“endobronchial ultrasound” OR “endobronchial ultrasound guided” OR “endobronchial ultrasound guided transbronchial needle aspiration” OR “EBUS” OR “EBUS-TBNA” OR “needle size”) |
| Timeframe | Until July 31, 2025 |
| Inclusion and exclusion criteria | Inclusion criteria: original article, research article, full paper, English language, adults, mention to subtype of malignant lymphoma |
| Exclusion criteria: editorial, comments, letters, proceeding, books, abstracts, non-English paper, less than 10 cases of malignant lymphoma diagnosed | |
| Selection process | First author conducted the selection process, initial literature review, assessed all of the identified studies based on the eligibility criteria. Both authors reviewed the final list of studies including in the review |
EBUS, endobronchial ultrasound; EBUS-TBNA, endobronchial ultrasound guided transbronchial needle aspiration.
Procedures
The diagnostic yields of EBUS-TBNA reported in the past decade are summarized in Tables 2,3. Three studies were conducted prospectively, and 11 were retrospective. In approximately 50% of the studies, EBUS-TBNA was performed under moderate sedation with midazolam and fentanyl or propofol, while general anesthesia was used in the remaining studies. Three studies employed 19G (Olympus and Boston Scientific), whereas 22G and/or 21G (mainly Olympus) were used in 12 studies, without crossover needle use. Rapid on-site cytological evaluation (ROSE) and flow cytometry were performed in most studies, depending on the bronchoscopists. Whether ROSE was performed by a cytologist or a pathologist varied depending on the institutions, and some articles mentioned these points while others did not.
Table 2
| Author | Year | Study design | Sedation | No. of passes | No. of patients with malignant lymphoma (D/R) | No. of patients with malignant lymphoma suspected or diagnosed by EBUS-TBNA (D/R) | No. of patients with malignant lymphoma defined the subtype by EBUS-TBNA (D/R) | ROSE | Flow cytometry |
|---|---|---|---|---|---|---|---|---|---|
| Herth (14) | 2008 | Prospective | General anaesthesia | 3 to 5 | 26 (–) | – | 9 (–) | – | – |
| Lim (9) | 2020 | Prospective | Unknown | Unknown | 23 (–) | 19 (–) | 15 (–) | + | + |
| Diab (15) | 2023 | Retrospective | General anaesthesia | Median 10 (range, 6–18) | 10 (6/4) | 5 (–) | 5 (–) | + | + |
–, insufficient information. D/R, de novo/recurrence; EBUS-TBNA, endobronchial ultrasound guided transbronchial needle aspiration; ROSE, rapid on-site cytological evaluation.
Table 3
| Author | Year | Study design | Sedation | Needle size | No. of passes | No. of patients with malignant lymphoma (D/R) | No. of patients with malignant lymphoma suspected or diagnosed by EBUS-TBNA (D/R) | No. of patients with malignant lymphoma defined the subtype by EBUS-TBNA (D/R) | ROSE | Flow cytometry |
|---|---|---|---|---|---|---|---|---|---|---|
| Herth (14) | 2008 | Prospective | General anaesthesia | 22 | 3 to 5 | 26 (–) | – | 3 (–) | – | – |
| Kennedy (5) | 2008 | Retrospective | General anaesthesia | 22 | 2 to 5 | 11 (3/8) | 10 (2/8) | 3 (2/1) | + | + |
| Steinfort (2) | 2010 | Retrospective | Unknown | 22 | Minimum 3 | 21 (2/19) | 16 (–) | 12 (–) | + | + |
| Marshall (16) | 2011 | Retrospective | General anaesthesia | 22 | Unknown | 11 (5/6) | 10 (4/6) | 8 (2/6) | + | + |
| Moonim (3) | 2013 | Prospective | Unknown | 22 | Mean 5.2 (range, 2–12) | 66 (51/15) | 63 (–) | 58 (–) | + | + |
| Senturk (1) | 2014 | Retrospective | Unknown | 22 | Median 3 (range, 2–6) | 14 (12/2) | 13 (11/2) | 11 (9/2) | – | – |
| Grosu (4) | 2015 | Retrospective | General anaesthesia | 22 | Median 5 (range, 3–19) | 75 (18/57) | 63 (14/49) | 58 (12/46) | + | + |
| Korrungruang (17) | 2016 | Retrospective | General anaesthesia 3/moderate sedation 16 | 21/22 | 6 | 19 (–) | 16 (–) | 6 (–) | + | – |
| Nason (18) | 2016 | Retrospective | Mostly general anaesthesia | Mainly 22 | Median 3 (range, 2–4) | 16 (9/7) | 8 (–) | 6 (–) | + | + |
| Plönes (19) | 2019 | Retrospective | General anaesthesia | 22 | 3 or 4 | 26 (–) | 5 (–) | 5 (–) | – | – |
| Dhooria (20) | 2019 | Retrospective | Mostly general anaesthesia | 21/22 | Median 3 (range, 2–4) | 33 (33/0) | 24 (24/0) | 8 (8/0) | + | + |
| Ray (21) | 2020 | Retrospective | Moderate sedation | 21/22 | 3 per station | 16 (7/9) | – | 6 (–) | – | – |
–, insufficient information. D/R, de novo/recurrence; EBUS-TBNA, endobronchial ultrasound guided transbronchial needle aspiration; ROSE, rapid on-site cytological evaluation.
Diagnostic yields of EBUS-TBNA using 19G
The details of the diagnostic yields of EBUS-TBNA using 19G are shown in Table 2. Lim et al. conducted a prospective study and reported a diagnostic yield of 65.0% (15/23 cases) (9). ROSE was performed in all cases, and tissue samples were sent for flow cytometry in 59.0% of cases. The number of needle passes and the sedation method were not specified. In a retrospective study, Diab et al. reported a diagnostic yield of 50.0% (5/10 cases), with 10 needle passes performed in over 50% of the cases (15). ROSE and flow cytometry were performed on demand, and detailed methods were not described. Notably, this study was conducted in a slightly different clinical setting, as EBUS-TBNA was performed before lymph node forceps biopsy. Herth et al. also conducted a prospective study in a similar clinical setting and reported a diagnostic yield of 35.0% (9/26 cases) under general anesthesia without ROSE or flow cytometry (14). However, this study did not specify the number of patients who underwent EBUS-TBNA using a 19G; therefore, the result does not represent the accurate diagnostic yield for 19G. In Addition, the needle used in this study was manufactured by Boston Scientific, rather than Olympus.
Diagnostic yields of EBUS-TBNA using 21G and 22G
The diagnostic yields of EBUS-TBNA using 21G and 22G are summarized in Table 3. Two studies were conducted prospectively, and 12 were retrospective. Plönes et al. reported a diagnostic yield of 19.0% (5/21 cases) under general anesthesia, without ROSE or flow cytometry, using three or four needle passes (19). This yield seemed relatively low; however, Senturk et al. reported a higher diagnostic yield of 71.4% (10/14 cases) in a retrospective study performed without ROSE or flow cytometry (1). Korrungruang et al. reported a subtype definition rate of 32.0% (6/26 cases) performed primarily under moderate sedation using ROSE with six needle passes (17). Even when both ROSE and flow cytometry were available, Dhooria et al. successfully diagnosed only 8/33 new-onset lymphoma cases (24.2%) (20). The study also included recurrent cases; however, subtype details were not provided; therefore, only new-onset cases were included in the present analysis. Nason et al. achieved a diagnostic yield of 37.5% (6/16 cases) using ROSE and flow cytometry, with a median of three passes (18). Steinfort et al. reported a diagnostic yield of 57.1% (12/21 cases), which was slightly higher than that reported in previous studies, although it was insufficient despite the use of ROSE and flow cytometry (2).
Conversely, in a previous study, Moonim et al. reported a diagnostic yield of 87.9% (58/66 cases) using 22G needles with ROSE and flow cytometry (3). The mean number of passes per lymph node was 5.2 (range, 2–12), and the sedation method was not specified. In a larger cohort, Grosu et al. performed EBUS-TBNA in 75 patients under general anesthesia, with ROSE and flow cytometry using a median of five punctures, and achieved a subtype definition rate of 77.0% (4). In addition, several smaller studies have been reported. Marshall et al. described a retrospective study showing a diagnostic yield of 72.7% (8/11 cases) with ROSE and flow cytometry under general anesthesia (16). In contrast, Kennedy et al. reported a diagnostic yield of 27.3% (3/11 cases) under similar research conditions (5). Finally, a retrospective study conducted by Ray et al. demonstrated a diagnostic yield of 62.5% (10/16 cases) using three passes per station. However, this study involved a small sample size and was conducted in a slightly different clinical setting, as EBUS-TBNA was performed before lymph node forceps biopsy (21).
Discussion
Notably, many clinical studies have investigated the diagnostic yields of EBUS-TBNA for malignant lymphoma, both in recent years and earlier. However, no randomized controlled trial has been conducted and only a few prospective studies have specifically compared needle sizes. Consequently, it is difficult to directly evaluate the relative effectiveness of different needle gauges. Furthermore, most available evidence is derived from retrospective studies; therefore, limitations such as incomplete data and selection bias are inevitable, complicating the interpretation of results.
Under these circumstances, we believe that the clinical issue is in determining whether EBUS-TBNA can define the histological subtype of malignant lymphoma. EBUS-TBNA is a convenient and safe procedure for detecting various cancers; however, recent advances in personalized medicine have increased the demand for larger and higher-quality tissue samples. In cases of malignant lymphoma, if the lymph node or lesion is confirmed to be involved but the subtype cannot be defined, a repeat or surgical biopsy, which will be more invasive, is recommended. Such delays may postpone the initiation of adequate treatment. Therefore, it is essential to obtain a definitive diagnosis, including subtype determination, in a single procedure whenever possible.
In this context, the findings of this review suggest that the diagnostic yield for lymphoma subtype determination using 19G and 21/22G needles will likely not differ when ROSE and flow cytometry are available. ROSE serves as a tool for cell count evaluation and diagnostic assistance. While in several reports, only cell count evaluation was mentioned, and it seemed to adequately play the role in determining whether specimens had been successfully obtained. Moonim et al. and Grosu et al. who analyzed many cases, support this finding. In principle, 19G needles also offer excellent flexibility, making resistance at the target lesions less of an issue (22), with no significant difference in complications (10). However, the studies employing 19G studies analyzed in this review showed a low diagnostic rate. Therefore, if ROSE and flow cytometry are available, and EBUS-TBNA was performed with 21/22G, we speculate that the difference in diagnostic rates compared with using 19G needles could be bridged. However, several studies using 21G or 22G even with ROSE and flow cytometry, reported relatively low diagnostic yields. Moreover, some studies did not specify the proportion of patients in whom ROSE and flow cytometry were employed, making their results difficult to interpret (for example, most reports did not mention the positivity and negativity of ROSE; therefore, many negative cases may have been included in some studies).
The feasibility of ROSE and flow cytometry depends on institutional resources; therefore, diagnostic strategies should be considered for settings in which these adjuncts are unavailable. Given the limited number of studies using 19G, it remains difficult to draw definitive conclusions; nonetheless, considering that diagnostic yields with 21G and 22G without ROSE and flow cytometry were often modest, using a 19G may be a reasonable alternative in certain clinical situations.
Ideally, the efficacy of different needle sizes should be evaluated through randomized controlled trials. Nevertheless, within the constraints of current clinical practice, the present review provides helpful insights into optimizing EBUS-TBNA for sampling mediastinal lesions in patients with suspected malignant lymphoma.
Regarding diagnostic yields, including sensitivity, it is reported that sensitivity is higher for recurrent malignant lymphoma cases than for initial malignant lymphoma diagnosis. However, in this review, studies using the 19G lack detailed information on this point, making comparison difficult; therefore, we did not address it here.
Finally, in recent years, the efficacies of endobronchial ultrasound-guided intranodal forceps biopsy (inserting forceps after EBUS-TBNA) (23) and endobronchial ultrasound-guided transbronchial mediastinal cryobiopsy (inserting cryoprobes) have been reported (24). However, most reports are based on analyses of small numbers of cases, and caution is warranted due to cost and technical issues. Furthermore, the examination methods differ from EBUS-TBNA, the details are not discussed in this review.
Conclusions
With the limited information on needles in past publications, in diagnosing the histological subtype of malignant lymphoma by EBUS-TBNA, it seems possibly to be no significant difference in diagnostic yield between 19G and 21/22G when ROSE and flow cytometry are performed concurrently.
Acknowledgments
We would like to thank Editage (www.editage.jp) for English language editing.
Footnote
Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://med.amegroups.com/article/view/10.21037/med-2025-1-53/rc
Peer Review File: Available at https://med.amegroups.com/article/view/10.21037/med-2025-1-53/prf
Funding: None.
Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://med.amegroups.com/article/view/10.21037/med-2025-1-53/coif). M.O. reports receiving speaker fees from Olympus Corporation and Fujifilm Corp. as a guest speaker at academic medical meetings. The other author has no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
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Cite this article as: Torii A, Oki M. Does needle size affect the diagnostic yield of endobronchial ultrasound-guided transbronchial needle aspiration for malignant lymphoma?—a narrative review. Mediastinum 2026;10:10.
