Tissue Adequacy and Diagnostic Yield Assessment in Malignant Lymph Nodes Using Endobronchial Ultrasound (EBUS)-Guided Miniforcep Biopsy vs. EBUS-Guided Transbronchial Needle Aspiration

Article information

Tuberc Respir Dis. 2025;88(3):545-556

Publication date (electronic) : 2025 April 3

doi : https://doi.org/10.4046/trd.2024.0134

Pipu Tavornshevin¹, Poonchavist Chantranuwatana², Vorawut Thanthitaweewat¹, Virissorn Wongsrichanalai¹, Thitiwat Sriprasart¹, Nophol Leelayuwatanakul^,1,3

¹Division of Pulmonary and Critical Care Medicine, Department of Medicine, Chulalongkorn University, Bangkok, Thailand

²Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

³Chulalongkorn Comprehensive Cancer Center, Department of Medicine, King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, Thailand

Address for correspondence Nophol Leelayuwatanakul Division of Pulmonary and Critical Care Medicine, Faculty of Medicine, Chulalongkorn University, 1873 King Chulalongkorn Memorial Hospital, Rama IV Road, Pathumwan, Bangkok 10330, Thailand Phone 66-2256-4000 ext. 81027 E-mail Nophol.L@chula.ac.th

Received 2024 September 13; Revised 2024 December 16; Accepted 2025 March 21.

Abstract

Introduction

Lung cancer remains the leading cause of cancer-related mortality globally, and personalized treatments based on histological features and oncogenic alteration serve as the cornerstone for managing advanced-stage cases. The demand for molecular testing, which facilitates targeted therapies, underlines the importance of collecting adequate samples. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive diagnostic tool that permits real-time visualization of mediastinal and hilar lymph node (LN) tissue sampling [1,2]. The diagnostic yield of EBUS-TBNA varies widely, ranging from 50% to 81%, and is contingent on factors such as the study population, diseases, procedural techniques, and cytological techniques [3-7]. A novel technique, EBUS-guided miniforcep biopsy (EBUS-MFB), uses MFB to obtain tissue from the mediastinal and hilar LNs [3]. A recent study indicates that this technique provides more adequate histological specimens, potentially increasing diagnostic yields and improving the value of the molecular analysis of lung cancer cases [5].

The adequacy of the tissue for molecular testing primarily depends on factors such as the absolute number of tumor cells and the proportion of tumor cells within the sample. The required tumor cell count (TCC) varies among different molecular markers. In particular, detecting epidermal growth factor receptor (EGFR) mutations requires a minimum of 1,000 cells, whereas identifying anaplastic lymphoma kinase (ALK)/ROS oncogene 1 (ROS1) translocations may require at least 100 cancer cells for adequate testing [8]. Concerning the tumor cell proportion, known as the neoplastic cell percentage (NCP), recent studies have indicated that a high proportion of non-tumor cells in samples can dilute tumor DNA, resulting in false-negative results [9,10]. The minimum requirements for NCP in genetic mutation testing remained undefined, varying according to the techniques used [11] and significantly differ among pathologists [10,12]. The adequacy of EBUS-TBNA samples for the molecular analysis of EGFR and ALK mutations has been confirmed [13]; however, research on tissue adequacy for molecular testing, particularly for newer methods such as next-generation sequencing (NGS), which require larger TCC and NCP, is limited. This is the first study to investigate the efficiency of the addition of EBUS-MFB to EBUS-TBNA in improving tissue adequacy based on these tumor cell characteristics in patients with malignant mediastinal and hilar lymphadenopathy, as compared with EBUS-TBNA alone.

Materials and Methods

2. Bronchoscopic techniques: EBUS-TBNA and EBUS-MFB

A convex-probe EBUS (CP-EBUS) bronchoscope (model BF-UC 180F and BF-UC190F, Olympus, Tokyo, Japan), connected to an ultrasound processor (EU-ME1, Olympus), was used to assess the mediastinal and hilar LNs before tissue sampling. The TBNA and MFB procedures were conducted in real-time at the index LN using the CP-EBUS bronchoscope. Each patient underwent EBUS-TBNA using a 21-gauge needle with an outer diameter of 0.82 mm (Model No. NA-201SX-4021, Olympus). The process involved 30 punctures per pass into the LN through the airway wall. The first TBNA pass was collected for traditional smear cytology for rapid-onsite evaluation (ROSE), followed by three additional TBNA passes. At the same TBNA puncture site, we used a guide sheath (GS) dilatation technique by advancing the TBNA GS against the bronchial wall to enlarge its diameter. A standard fenestrated miniforcep with an external diameter of 1.5 mm (Model No. FB-233D, Olympus) was then introduced through the endoscope’s working channel. The miniforcep was advanced through the puncture site into the LN, visible on the ultrasound image. After penetration, the miniforcep was opened, slightly advanced, closed, and retracted to biopsy the LN tissue (Figure 1). Three samples were collected using the MFB. EBUS-TBNA and EBUS-MFB were performed where feasible in cases with multiple mediastinal and hilar LNs. All procedures were performed by experienced, board-certified interventional pulmonologists.

Fig. 1.

Endoscopic view of lymph node biopsy and endobronchial ultrasound procedure. (A) Image depicts the puncture site created by the transbronchial needle aspiration needle’s guide sheath. (B) Image illustrates the miniforcep, extended from the working channel, penetrating the bronchial wall and entering the right interlobar space. (C) Image presents the endobronchial ultrasound image of the right interlobar lymph node, with the opening of the miniforcep clearly visible within the lymph node. (D) Image displays the miniforcep being opened and slightly advanced for lymph node tissue biopsy.

Bleeding severity during the procedures was categorized as either minor or major. Minor bleeding was a bleeding managed by routine bronchoscopic procedures, such as suction, cold saline, or adrenaline instillation. Major bleeding refers to cases requiring blood transfusion. Further, the occurrence of pneumothorax or pneumomediastinum, respiratory failure, hemodynamic instability, or unscheduled hospital admission was recorded. The procedure was promptly discontinued if any complications occurred. After the procedure, patients were monitored for 1 hour in the recovery room and a chest radiograph was conducted to track any complications such as pneumothorax, pneumomediastinum, or other procedure-related adverse events. Further, patients were contacted by phone between 48 and 96 hours postprocedure to determine any symptoms of chest pain, hemoptysis, blood-stained sputum, or the need for hospital revisit.

Results

This study enrolled 83 patients with enlarged intrathoracic LNs. However, 14 patients were subsequently excluded from the protocol for various reasons: eight due to miniforcep penetration failure of the index LN, two due to significant bleeding after EBUS-TBNA, three due to EBUS-determined LN sizes of <10 mm, and one due to intolerance of bronchoscopy caused by severe coughing during EBUS-TBNA (Figure 2). This study included the remaining 69 patients, with a mean age of 64.1±11.7 years (68.1% males). Of these, 31 (44.9%) had underlying malignancies, including lung cancer (17.3%), breast cancer (7.2%), colorectal cancer (5.8%), head and neck cancer (5.8%), lymphoma (4.3%), and other cancer types (4.3%). Table 1 shows additional information regarding other medical illnesses.

Fig. 2.

Diagnostic flow diagram. *No lymphoid stroma and no specific diagnosis. EBUS: endobronchial ultrasound; TBNA: transbronchial needle aspiration; MFB: miniforcep biopsy; LN: lymph node.

Table 1.

Baseline characteristics of patients with mediastinal and hilar lymphadenopathies and radiographic characteristics and sonographic findings of the index lymph node

Both EBUS-TBNA and EBUS-MFB were successfully employed to biopsy 74 index LNs. The majority of these nodes were observed in the subcarinal region (52.7%), with the remaining distributed among the right lower paratracheal (27%), right interlobar (13.5%), left interlobar (5.4%), and left lower paratracheal (1.4%) regions. The mean size of the index LN, identified by chest CT scans, was 15.4 mm (range, 10 to 29), whereas the mean size based on EBUS results was 19.7 mm (range, 10.1 to 34.2). Radiographic findings revealed necrosis of the nodes in 23%, the presence of calcification in 4.1%, and a fatty hilum in 4.1% of nodes. EBUS results revealed that 52.7%, 73.9%, 52.7%, 60.8%, and 44.6% of the nodes demonstrated a round shape, heterogeneous echogenicity, distinct margin, lacked a central hilar structure, and presence of vascular structure, respectively (Table 1). Using EBUS-TBNA, 41 (55.4%) nodes were diagnosed as malignant, whereas EBUS-MFB diagnosed 32 nodes as malignant. Of the 41 LNs diagnosed as malignant using EBUS-TBNA, 26 (63.3%), four (9.8%), five (12.2%), four (9.8%), and two (4.9%) were determined as lung adenocarcinoma, breast adenocarcinoma, poorly differentiated carcinoma, small cell lung carcinoma, and lymphoma, respectively.

Discrepancies in cases of malignant mediastinal and hilar LNs were observed in three (9.4%) out of 32 cases, requiring a third blinded interpretation. A concordance existed between EBUS-TBNA and EBUS-MFB for tissue adequacy in 30 of the 32 nodes. The analysis revealed comparable tissue adequacy between EBUS-TBNA (30 of 32 nodes, 93.8%) and EBUS-MFB added to EBUS-TBNA (31 of 32 nodes, 96.9%; p=0.317) (Table 2). The marginal homogeneity test revealed a significant difference in TCC between EBUS-TBNA and EBUS-MFB (p=0.015) but with no significant difference in NCP (p=0.233) (Supplementary Tables S1, S2). No statistical differences were found when analyzing cases where the TCC was >100 cells or the NCP was >25% between EBUS-TBNA and EBUS-MFB (p=0.655 and p=0.102, respectively) However, EBUS-TBNA caused a higher TCC, with >1,000 cells in 27 (84.4%) of 32 cases compared to EBUS-MFB in 17 (53.1%) of 32 cases (p=0.004) (Supplementary Table S3).

Table 2.

Tissue adequacy between EBUS-TBNA and EBUS-MFB added to EBUS-TBNA specimens

Of the 74 LNs obtained, all but one case yielded adequate histology and a confirmed diagnosis from histological analyses. In one case, the EBUS-TBNA technique resulted in an inadequate tissue biopsy, demonstrating a small amount of crushed lymphoid tissue, whereas the EBUS-MFB exhibited bronchial tissue. A follow-up CT scan conducted on this case after 1 year demonstrated no significant change in the mediastinal and hilar lymphadenopathy, indicating a benign condition. The overall diagnostic yield of EBUS-TBNA was 66 (89.2%) out of 74 nodes. Initially, seven nodes in the EBUS-TBNA group remained undiagnosed, but diagnoses were later determined using EBUS-MFB. The pathological results of these undiagnosed cases revealed three anthracotic LNs, two nodes with tuberculous lymphadenitis (Figure 3A, B), one node with lymphoma, and one silicotic node. Conversely, the overall diagnostic yield of EBUS-MFB was 50 (67.5%) out of 74 nodes. Within this group, 23 nodes remained undiagnosed due to inadequate specimens, which included 13 cases of no lymphoid stroma, five cases of fibroadipose tissue, four cases of bronchial tissue, and one case of uncertain cell composition. Combining EBUS-MFB with EBUS-TBNA significantly increased the overall diagnostic yield from 89.2% to 98.6% (p=0.014) (Table 3). However, this combined technique did not increase the diagnostic yield in malignant cases. Only one node, which was initially categorized as non-diagnosed using the EBUS-TNBA technique, was diagnosed as diffuse large B-cell lymphoma using the EBUS-MFB method (Figure 3C, D). This combined technique yielded a diagnostic in 97% of cases, compared to 78.8% when using EBUS-TBNA alone for non-malignant diseases (p=0.014). Among the 32 LN diagnosed with non-malignant disease using combined techniques, the pathological results indicated 11 anthracotic, 11 reactive lymphadenopathy, six tuberculous lymphadenitis, three silicotic, and one sarcoidosis. Two undiagnosed cases of EBUS-TBNA were diagnosed with granulomatous disease using EBUS-MFB.

Fig. 3.

Sampling node from discordant case between endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and EBUS-miniforcep biopsy (MFB). (A, B) Images illustrate samples from a patient with tuberculous lymphadenitis. The TBNA specimen in (A) presents entirely granular eosinophilic necrotic material without any granuloma (original magnification ×400). In contrast, the MFB specimen in (B) demonstrates an area of necrosis with a vague aggregate of epithelioid histiocyte, suggestive of granulomatous inflammation (original magnification ×400). (C, D) Image illustrate samples from patient with diffuse large B-cell lymphoma. In (C), the TBNA specimen shows small fragments of crushed lymphoid stroma (original magnification ×400), while (D), the MFB specimen, reveals diffuse, highly cellular infiltration of malignant small round cells, thereby confirming a lymphoma diagnosis with adequate tissue sample.

Table 3.

Diagnostic yield of EBUS-TBNA, EBUS-MFB, and combined approach

Discordant diagnoses between EBUS-TBNA and EBUS-MFB for non-malignant diseases were observed in 20 (62.5%) of the 32 nodes. Fourteen nodes were diagnosed using EBUS-TBNA but remained undiagnosed by EBUS-MFB because of various pathological results, including the absence of lymphoid stroma in seven nodes, the presence of fibroadipose tissue in four nodes, bronchial tissue in two nodes, and uncertain cell composition in one node. Conversely, six nodes were misdiagnosed with EBUS-TBNA were accurately diagnosed with EBUS-MFB (Supplementary Table S4). The detail of pathological results in all discordant cases were shown in Supplementary Table S5.

Univariable analysis revealed that patients with radiographic evidence of a necrotic node were more likely to have a successful biopsy using EBUS-MFB. Notably, the presence of a necrotic node on chest CT scans was related to an increased likelihood of successful biopsy using EBUS-MFB with an OR of 14.72 and 95% CI of 1.99 to 636.03 (p=0.002) (Supplementary Table S6).

The mean duration of the EBUS-TBNA and EBUS-MFB procedures was 37.55±13.16 minutes. The medications administered during the procedure included intravenous fentanyl, intravenous midazolam, and topical lidocaine with a mean dose of 87.13±36.95 μg, 3.85±1.72 mg, and 121.86±40.49 mg, respectively. The overall complication rate was 2.9%. The only acute complication reported was minor bleeding during the EBUS-MFB procedure, which was successfully controlled by the endobronchial instillation of epinephrine. No severe complications, such as pneumothorax, pneumomediastinum, respiratory failure, or hemoptysis, were observed (Supplementary Table S7). Delayed symptoms included blood-stained sputum (5.8%) and chest pain (2.9%), which did not require medical attention.

Discussion

Ensuring tissue adequacy is crucial for reliable molecular analysis, as it requires an adequate quantity and percentage of tumor cells. Currently, EBUS-TBNA is a standard technique for assessing enlarged mediastinal and hilar LNs. However, its limited sample volume poses a challenge for molecular analysis in some cases of malignant diseases. This study is the first to compare tissue adequacy between samples obtained using the conventional TBNA and MFB techniques, added to TBNA under real-time EBUS guidance. Interestingly, our results revealed that adding EBUS-MFB, which theoretically provides larger specimens, to EBUS-TBNA did not increase tissue adequacy compared with EBUS-TBNA alone. This indicates that the specimens obtained from EBUS-TBNA are adequately sufficient for various molecular analysis methods. However, the combination of EBUS-MFB and EBUS-TBNA significantly increases the diagnostic yield in patients with non-malignant mediastinal and hilar lymphadenopathy.

Routine mutation analyses in current clinical practice target specific mutations such as EGFR, ALK, ROS1, Kirsten rat sarcoma virus (KRAS), and rearranged during transfection (RET) [15-17]. A prior meta-analysis study revealed that EBUS-TBNA samples provide high diagnostic adequacy for EGFR and ALK mutation analyses, with pooled probabilities of obtaining sufficient samples being 94.5% and 94.9%, respectively [13]. However, these studies did not specifically address tissue adequacy in terms of TCC and NCP. Our study defined tissue as adequate if it met both the criteria of having a TCC of >100 cells and NCP of >25%. This predefined criterion considers that different molecular analysis tests have varying minimum tissue adequacy requirements. In particular, pyrosequencing requires at least 10% of NCP, direct sequencing requires 25% of NCP, whereas some reverse transcription real-time polymerase chain reaction tests are only applicable to tumor specimens with an NCP of at least 30% [11]. Notably, our study revealed no significant difference in tissue adequacy between samples from the combination of EBUS-MFB and EBUS-TBNA and those from EBUS-TBNA alone. This indicates that tissue samples obtained solely from EBUS-TBNA may be suitable for various molecular analysis methods.

The number of TBNA passes may serve as a pivotal factor in identifying tissue adequacy, considering that the American College of Chest Physicians Clinical Practice Guideline for the Acquisition and Handling of Endobronchial Ultrasound Transbronchial Needle Samples recommends ≥4 needle passes, although this is supported by a low level of evidence [18]. Previous studies that investigated the number of TBNA passes and the success rate of molecular testing primarily focused on the final testing outcomes. However, our study applied adequacy criteria to assess the qualifications of sample tissue through each method, comprising either four TBNA passes using ROSE or three attempts of MFB per site, instead of solely depending on the success of molecular testing. Our subgroup analysis revealed that tissue obtained via TBNA met the adequacy criteria more frequently than that obtained from MFB, based on TCC and NCP metrics. With four needle passes and the use of ROSE, EBUS-TBNA yielded a significantly greater number of tumor cells (exceeding 1,000 cells) in 84% of cases, with NCP of >25% in 93.8% of cases. Similar to our results, a particular study assessed the association between the number of passes and the success rate of molecular testing, demonstrating that the success rates could reach up to 82.95% with three needle passes and up to 100% through four needle passes [19]. This indicates that four needle passes could be sufficient for molecular testing. However, increasing the number of TBNA passes could produce a larger quantity of tumor cells, particularly for molecular techniques that require a significant amount of tumor DNA. Moreover, a recent study by Murakami et al. [20] demonstrated the highest TCC from EBUS-TBNA samples compared to endobronchial biopsy and small and large endobronchial ultrasound with GS samples using the Oncomine Dx Target Test for NGS. Theoretically, a larger biopsy tissue size, such as that obtained from EBUS-MFB, could overcome this limitation. However, our study revealed that the sample tissue obtained by EBUS/MFB exhibited lower rates of achieving the tissue adequacy criteria. This is related to the repetitive punctures per pass during EBUS-TBNA, which likely more effectively improves the volume of tumor cell collection than EBUS-MFB. Consequently, the addition of EBUS-MFB did not markedly enhance tissue adequacy.

Previous studies have revealed the superiority of EBUS-MFB over EBUS-TBNA alone [3,5,7,21,22]. In particular, Chrissian et al. [3] reported a significantly higher overall diagnostic accuracy of 97% with the combined approach compared to 81% for EBUS-TBNA and 91% for EBUS-MFB alone in a study of 50 patients with mediastinal or hilar lymphadenopathies. A retrospective cohort study by Wang et al. [23] involved 227 patients and revealed similar diagnostic yields for EBUS-TBNA (95%) and EBUS-MFB (94%). However, discordant diagnoses were observed between EBUS-TBNA and EBUS-MFB in 19 (8.37%) of 227 cases [23]. Earlier studies reported a pooled overall diagnostic yield of 67% for EBUS-TBNA and 92% for the combination of EBUS-TBNA and EBUS-MFB [21]. Consistent with the findings of these studies, our results confirm that adding EBUS-MFB to EBUS-TBNA is superior to EBUS-TBNA alone, thereby significantly increasing the overall diagnostic yield from 87.7% to 98.2%.

Chrissian et al. [3] reported comparable diagnostic yields between MFB and TBNA in non-malignant diseases, whereas our study observed a lower diagnostic yield in the MFB group for non-malignant conditions primarily due to a higher proportion of inadequate specimens. Notably, this study categorized the outcomes as either diagnostic or non-diagnostic, without specifically addressing the inadequate specimens [3]. In contrast, our study determined specific cases of inadequate specimens, such as those lacking lymphoid stroma, containing only fibroadipose tissue or bronchial tissue, or exhibiting uncertain cellular composition. Furthermore, the diagnostic yield of TBNA in the study of Chrissian et al. [3] appeared lower than that typically reported in the literature. This discrepancy is likely associated with the relatively low proportion of non-lung cancers within the study population. In contrast, our study revealed a high diagnostic yield of 98% for malignant disease in the TBNA group, despite a similar proportion of non-lung cancers as the study of Chrissian et al. [3], indicating that patient population characteristics, such as the prevalence of specific cancer types, may significantly affect the diagnostic yield of TBNA. Examining the tissue architecture from larger tissue samples may be crucial for accurately diagnosing certain disorders, including granulomatous diseases, silicosis, and lymphoproliferative diseases. The discordant diagnoses observed in our study, where MFB provided superior diagnostic results, supported this finding. Notably, various factors affect the diagnostic yield of EBUS-MFB, including the type and size of the forceps used, the tissue sampling technique employed, the size of the LN, and the expertise and practices of the cytopathology laboratory.

A systematic review and meta-analysis revealed that patients undergoing both EBUS-TBNA and EBUS-MFB experienced an overall complication rate of approximately 3% to 4% [21]. Complications included Ray et al. [6] reported a high incidence of pneumothorax and pneumomediastinum, which was attributed to transbronchial lung biopsy. Notably, they used an electrocautery knife to create a hole for intranodal forcep biopsy, whereas other studies that did not utilize an electrocautery knife reported lower pneumomediastinum complication rates. Further, Radchenko et al. [7] reported one postprocedure death due to an underlying cardiac condition. Compared with other interventions, EBUS-guided LN sampling is considered less invasive and associated with lower morbidity than mediastinoscopy [24]. In our study, we demonstrated a relatively low complication rate, with minor bleeding as the only complication. No cases of pneumothorax or pneumomediastinum were determined during follow-up chest X-rays 1 hour after the procedure. Moreover, delayed symptoms, such as chest pain and blood-stained sputum, occurred in only 10% of cases, which resolved spontaneously within 96 hours with conservative treatment. Based on these results, we conclude EBUS-MFB, performed using the GS-dilatation technique, as a safe procedure with a low complication rate. However, we revealed that only the necrotic LNs determined on imaging had a higher likelihood of a successful MFB.

Our study has several strengths that improve its validity. First, we used readily available miniforceps from a GS kit, specifically designed for radial probe EBUS-guided transbronchial biopsy. This type of forceps differs from those used in previous studies; however, it has been successfully employed without requiring specialized forceps. Second, our results demonstrate that the GS-dilatation technique is safe, feasible, and efficient for performing intranodal forceps biopsy. Notably, this technique eliminates the need for an electrocautery knife, which is typically associated with a higher complication rate. Third, we applied predefined TCC and NCP criteria to ensure tissue adequacy. These criteria are predominantly used in various molecular analysis methods, indicating that our suitability criteria could be broadly applied across different molecular analysis techniques. Finally, we ensured stringent validation of all pathologic results, thereby further underscoring the reliability of our results, as evidenced by low discrepancies across all cases.

However, this study has certain limitations. First, the applied tissue adequacy criteria in our study do not guarantee the success of the molecular analysis, particularly NGS, as various factors affect the success rate. We did not measure the tumor surface area, which has been reported as another factor influencing successful NGS analysis [20]. Considering the ongoing debate regarding the suitability criteria for tissue used in NGS analysis, further studies are warranted to establish validated standards for tissue adequacy across different NGS methods. Second, the diagnostic yield observed in our study may differ from that reported in other studies due to variations in patient populations and disease prevalence. In cases of non-malignant diseases presenting with non-specific results, we relied on chest CT scans conducted 6 to 12 months postprocedure to identify the non-malignant etiology, rather than pursuing more invasive surgical assessments such as thoracotomy or video-assisted thoracoscopic surgery. Furthermore, a significant proportion of patients with confirmed malignancy may receive cancer-directed therapy, such as chemotherapy, targeted therapy, or immunotherapy, even in the absence of discernible metastatic involvement within the LNs. Suspected metastatic LNs that exhibited no appreciable growth on follow-up imaging may have demonstrated a partial response to treatment, rather than representing truly nonmetastatic nodal involvement. These factors may have affected the overall diagnostic yield observed in our study. Third, we encountered cases of unsuccessful MFB techniques. The GS-dilatation technique posed a significant challenge when attempting to penetrate the LN. Ideally, LNs located at the bifurcation points, such as the subcarinal region or interlobar region, are easier to access due to the needle’s perpendicular position relative to the airway wall. This could introduce bias in selecting LNs with a higher likelihood of successful MFB.

In conclusion, this study assessed tissue adequacy according to histological tumor cell characteristics, including TCC and NCP, and compared EBUS-TBNA alone with the combination of EBUS-MFB and EBUS-TBNA. Our results revealed no significant difference between the two methods, although EBUS-TBNA yielded a significantly large number of tumor cells. This supports the hypothesis that EBUS-TBNA alone may be sufficient to provide an adequate specimen for molecular analysis. Furthermore, our results indicate that intranodal forceps biopsy using the GS-dilatation technique is safe, feasible, and efficient. The combination of EBUS-MFB with EBUS-TBNA could improve the diagnostic yield in cases of non-malignant mediastinal and hilar lymphadenopathy.

Supplementary Material

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