Lung cancer may present either as a parenchymal. Utility of Transbronchial Needle Aspiration in the Diagnosis of Endobronchial Lesions*

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1 Utility of Transbronchial Needle Aspiration in the Diagnosis of Endobronchial Lesions* Asok Dasgupta, MBBS, Prasoon Jain, MBBS, MD; Omar A Minai, MBBS; Sunder Sandur, MD; Yvonne Meli, RN; Alejandro C. Arroliga, MD, FCCP; and Atul C. Mehta, MBBS, FCCP Background: The utility of transbronchial needle aspiration (TBNA) in visible endobronchial lesions presenting as either an exophytic mass lesion (EML) or submucosal and peribronchial disease (SPD) is not well established. Objective: To compare the yield of conventional diagnostic procedures (CDP) (bronchial washing, bronchial brushing, and endobronchial forceps biopsy) with that obtained from a combination of CDP and TBNA (CDP TBNA). Design: Prospective study of 55 patients. Setting: Tertiary-care referral hospital. Results: Of the 55 patients in whom malignancy was confirmed, CDP TBNA identified 53 (96%) vs 42 (76%) identified by CDP (p 0.001). The highest yield from any individual procedure was obtained by TBNA. Of the 23 patients with SPD, 22 (96%) were diagnosed using CDP TBNA compared with 15 (65%) by CDP (p 0.016); the yield from TBNA alone (22 of 23) in this group surpassed the combined yield from all other procedures. Although no statistically significant difference in yield was observed for EML, the use of TBNA identified four additional patients compared with CDP. Conclusion: We conclude that the addition of TBNA to CDP increases diagnostic yield in patients with visible endobronchial lesions. (CHEST 1999; 115: ) Key words: endobronchial lesion; exophytic mass lesion; submucosal and peribronchial disease; transbronchial needle aspiration Abbreviations: BB brush biopsy; BW bronchial washings; CDP conventional diagnostic procedures; CDP TBNA combination of conventional diagnostic procedures and transbronchial needle aspiration; EBB endobronchial forceps biopsy; EML exophytic mass lesion; SPD submucosal and peribronchial disease; TBNA transbronchial needle aspiration Lung cancer may present either as a parenchymal lesion or as endobronchial disease. The latter may manifest as an exophytic mass lesion (EML), submucosal infiltration, or extrinsic compression from peribronchial disease. These presentations may also be associated with metastasis to the hilar or mediastinal lymph nodes. The use of transbronchial needle aspiration (TBNA) in the staging of lung *From the Department of Pulmonary and Critical Care Medicine (Dr. Dasgupta), Kelsey-Sebold Clinic, Houston, TX, and the Department of Pulmonary and Critical Care Medicine (Drs. Jain, Minai, and Sandur, Ms. Meli, and Drs. Arroliga and Mehta), Cleveland Clinic Foundation, Cleveland, OH. Presented in abstract form at the annual session of the American Thoracic Society, Chicago, IL, April 28, Manuscript received June 25, 1998; revision accepted December 19, Correspondence to: Atul C. Mehta, MBBS, FCCP, Department of Pulmonary and Critical Care Medicine, Desk A-90, Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH cancer and in the diagnosis of peripheral lesions has been well documented. 1,2 However, its utility in endobronchial lesions has not been substantiated. Possibly the higher yield obtained from endobronchial forceps biopsy (EBB) has precluded its use in EML. 3 5 Despite the poor yield from EBB and the reported higher yield with the use of TBNA in submucosal and peribronchial disease (SPD), 6 the use of TBNA has been quite restricted. We prospectively investigated the diagnostic yield by conventional diagnostic procedures (CDP) with that obtained by the combination of CDP and TBNA (CDP TBNA) in the evaluation of patients with endobronchial lesions (EML and SPD). Materials and Methods Patients found to have EML or SPD during routine fiberoptic bronchoscopy were entered in the study. Patients with preexist- CHEST / 115 / 5/ MAY,

2 ing known malignancy were excluded. Submucosal disease was defined as erythema, vascular flares, enhanced rugal pattern, thickening or loss of mucosal markings, and bronchial narrowing. Peribronchial disease was defined as luminal narrowing secondary to extrinsic compression. All patients had bronchial washings (BW), brush biopsy (BB), EBB, and TBNA. The procedural sequence between EBB and TBNA was randomly allocated to either of the two sequences: (1) BW, EBB, TBNA, and BB, or (2) BW, TBNA, EBB, and BB. Four adequate EBB specimens and two passes with the cytology needle (21- or 22-gauge; Mill-Rose Lab, Inc; Mentor, OH) were performed. Specimen handling, cytopathology evaluation, and technical details of TBNA have been described elsewhere. 1 Both smear preparation and flushed aspirates were sent for cytology; rapid on-site cytology evaluation was not performed. For obtaining specimens from EML, the needle was directly inserted into the lesion, avoiding necrotic areas as practiced with other CDP. For submucosal lesions, the needle was partially introduced at an angle of 45 into the bronchial wall, whereas complete penetration through the wall was performed in the case of extrinsic compression from peribronchial disease. 1 The bronchoscopic findings were correlated with the anatomic location of the peribronchial lesion on CT scans of the chest, when available. BW and BB were performed in a conventional fashion. Cytologic analysis was considered positive only when large numbers of definitely malignant cells were present. Cellular atypia and abnormal cells highly suggestive of malignancy were considered as negative, because they failed to serve as diagnostic end points. The primary outcome measure studied was the diagnostic yield comparing CDP (combination of BW, BB, and EBB) with CDP TBNA. Furthermore, we analyzed the impact on diagnostic yield from each of the individual procedures as well as on the basis of the nature of the lesion, ie, EML or SPD. We also studied whether presence of lesion in upper lobes and sequence of performing TBNA and EBB influenced diagnostic yield. Any procedure-related complications and damage to the bronchoscope were also documented. Statistical analysis of the difference in diagnostic yield between the two groups was performed using McNemar s test. Fisher s Exact Test was used to detect any difference between locations and procedure sequence. A p value 0.05 was considered to be significant. Results During a 15-month period, 58 patients were enrolled in the study (Fig 1). Three patients were excluded two because of benign lesions (one with granulation tissue and one with benign sinus histiocytosis on mediastinoscopy), and one patient refused further investigations. Of the 55 eligible patients, 32 (58%) had EML and 23 (42%) had SPD. Malignancy was confirmed by Figure 1. Diagnostic outcomes. Filled diamond: benign, 2 patients; declined investigation, 1 patient. Asterisk: lung cancer, 52 patients; lymphoma, 1 patient; spindle cell carcinoma, 1 patient; melanoma, 1 patient Clinical Investigations

3 bronchoscopy in 53 patients 1 patient had metastatic malignant melanoma and 52 patients had primary lung cancer. The two patients with undiagnosed disease were found to have diffuse B-cell lymphoma and spindle cell tumor by transthoracic needle biopsy specimen and wedge resection, respectively. Thus, all 52 patients with lung cancer had their conditions diagnosed by a combination of bronchoscopic techniques. For the 55 eligible patients, the diagnostic yields from CDP and CDP TBNA are depicted in Table 1. There was a significant increase in diagnostic yield with the addition of TBNA (CDP, 76%; CDP TBNA, 96%; p 0.001), primarily resulting from differences in the SPD group (CPD, 65%; CPD TBNA, 96%; p 0.016). Although no statistical difference was observed in the EML group, TBNA did identify four additional patients with lung cancer. Table 2 demonstrates the different diagnostic yields from individual procedures and their combination thereof. The highest individual yield was obtained by TBNA. There were significant differences in the yield from TBNA in the SPD group compared with EBB (p 0.004) and BB (p 0.001). The individual yield of TBNA in the latter group surpassed the combined yield from CDP, respectively: 22 of 23 vs 15 of 23. TBNA was exclusively diagnostic in 11 patients (20% of all patients): 7 patients with SPD (30% of SPD patients); and 4 patients with EML (13% of EML patients). Of these four patients with EML, there were two patients with small cell carcinoma who had crush artifacts on the EBB and were solely diagnosed by TBNA. BB and EBB, respectively, were each exclusively diagnostic in two patients (6%) and one patient (3%) with EML; the positive EBB was obtained from a patient who had carcinoma in situ. BWs were never positive in situations in which all other procedures were negative. Analysis of diagnostic yield as a function of location of the lesion is shown in Table 3. Of the 55 lesions, 25 (45%) were in the upper lobes: 15 (27%) in the right upper lobes and 10 (18%) in the left upper lobes. The addition of TBNA increased yield irrespective of the location of the lesion in the upper Table 2 Diagnostic Yield From Individual Procedures and Their Combinations* Procedures EML (n 32) SPD (n 23) or other lobes. However, there was no statistical advantage in performing TBNA in the upper lobes compared with other lobes. Nor were there any differences in yield observed within the CDP group between the upper and other lobes. Similarly, no difference in diagnostic yield was seen whether TBNA was performed before or after EBB (Table 4). Results from distribution of malignant cell types obtained by cytologic assessment from TBNA were in complete concordance with those obtained by histologic assessment by EBB. Minor bleeding was observed in three patients, two after EBB and one after TBNA. The use of TBNA did not result in any damage to the bronchoscope in this series. Discussion Total (n 55) Exclusively Diagnostic BW 10 (31) 5 (22) 15 (27) 0 (0) BB 19 (59) 11 (48) 30 (55) 2 (6) EBB 23 (72) 10 (43) 33 (60) 1 (3) TBNA 25 (78) 22 (96) 47 (85) 11 (20) EBB BB 26 (81) 14 (61) 40 (73) EBB TBNA 27 (84) 22 (96) 49 (89) TBNA BB 30 (94) 22 (96) 52 (95) EBB BB TBNA 31 (97) 22 (96) 53 (96) *Values given as No. (%). Only a small number of investigators have addressed the issue of TBNA in EML or SPD The yield from EBB for EML has been reported to be between 67% and 100% in different series. 3 5,7 10 The yield could be decreased if there is surface necrosis of the tumor, sampling error, or inadequate tissue, or in the presence of crush artifacts. Similarly, the yield from BB and BW has been demonstrated to be between 55% and 93%, 3,7 10,12 and 0% and 63%, 7,9,10,12 respectively. Furthermore, reported yield from TBNA has varied between 65 and 92% in three published studies using a variety of nee- Table 3 Diagnostic Yield on the Basis of Location Table 1 Diagnostic Yield From CDP vs CDP TBNA Condition CDP, No. (%) CDP TBNA, No. (%) p Value* Total (n 55) 42 (76) 53 (96) EML (n 32) 27 (84) 31 (97) 0.16 SPD (n 23) 15 (65) 22 (96) *McNemar s test. Site CDP CDP TBNA p Value* Upper lobes (n 25) RUL (n 15) LUL (n 10) Other lobes (n 30) *Fisher s Exact Test. Within same procedure group, upper lobes vs other lobes, p 1.0 (not significant). RUL right upper lobe; LUL left upper lobe. CHEST / 115 / 5/ MAY,

4 Table 4 Diagnostic Yield on the Basis of TBNA/EBB Sequence Condition TBNA Before EBB, No. of Patients (n 29) TBNA After EBB, No. of Patients (n 26) p Value* EML SPD *Fisher s Exact Test. dles Our yield in EML, using the EBB, BB, BW, and TBNA, respectively, has been 72%, 59%, 31%, and 78%, which is consistent with the published results. Submucosal disease, as defined earlier, and peribronchial disease presenting as narrowing and extrinsic compression, on the other hand, have significantly lower yields with CDP. 6,8,9 Although Lundgreen et al 9 reported a greater yield with EBB than TBNA (69% vs 46%), in two other studies, these trends were reversed. 6,8 Shure and Fedullo 6 showed an increased yield with TBNA (71%) compared with EBB (55%), similar to results obtained by Buirski et al 8 (EBB, 43%; TBNA, 100%). The individual yield from EBB and TBNA in our series (EBB, 43%; TBNA, 85%) is similar to that reported in the latter series. The addition of TBNA to CDP increased the diagnostic yield in our series. In submucosal disease, involvement tends to occur in a submucosal plane along the lymphatics with minimal mucosal abnormality. Similarly, extrinsic compression from peribronchial disease tends to leave the mucosal surface predominantly intact. Conventional procedures using EBB or BB tend to sample mainly the surface rather than deep within the lesion. In these situations, the ability of TBNA to provide adequate sampling by penetrating either the submucosa or directly through the bronchial wall into the tumor mass could enhance diagnostic yield. Our diagnostic yield of 65% with CDP, compared with the 96% yield obtained by the addition of TBNA, is probably a reflection of this anatomic variation that occurs with SPD. Similar reasoning probably explains a negative TBNA result in the patient with carcinoma in situ, in whom EBB was the only positive result. A similar increase in diagnostic yield was observed in EML when TBNA was added to CDP. Although this increase did not reach statistical significance, it diagnosed lung cancer in four additional patients. The potential for TBNA to bypass surface necrosis and sample viable tumor from deep within the mass is a possible explanation. Moreover, the particular cell type of the tumor could influence yield from EBB. Crush artifacts produced during biopsy sampling of small cell cancer may result in a negative result. This situation was seen in two of the cases in which TBNA was exclusively diagnosed. Jones et al 13 have similarly reported on the critical diagnostic value of TBNA in five patients with small cell cancer who demonstrated crush artifacts on nondiagnostic EBB. Analysis of yield from individual procedures and their combinations revealed several interesting facts. The best yield from any individual procedure was obtained with TBNA. In SPD, the yield from TBNA was far superior to the yield from any other individual procedure or their combination. Thus, use of TBNA alone or in combination with CDP would have diagnosed disease in all these patients, ie, the critical information was provided by TBNA alone. In EML, progressively higher yield was obtained by the addition of TBNA to EBB and BB, with the best results being obtained by a combination of EBB, BB, and TBNA. BW provided the least diagnostic information and were never positive when any of the other test results were negative. The ability of BW to enhance yield has been questioned before. Kvale et al 7 found no additional advantage in performing BW when forceps biopsy and BB were simultaneously performed. However, as shown in Table 2, the addition of BW did increase the yield in EML from 26 to 27 of 32 cases (81 to 84%) and in SPD from 14 to 15 of 23 cases (61 to 65%) if TBNA was not performed. Thus, if TBNA is used as part of the sampling procedures, there is no advantage in performing simultaneous BW. We also analyzed diagnostic yield as a function of the location of the lesion. Traditionally, lesions in upper lobes are often technically difficult to access because of the acute angulation of the bronchoscope needed to reach them, thus restricting adequate sampling by the forceps. Buirski et al 8 have reported on 28 upper lobe lesions, 17 of which were proximal at the lobar orifice, 11 being distal. Of the 17 proximal lesions, 14 were diagnosed by EBB, but only 4 of 11 distal lesions were identified by the EBB compared with 10 of 11 by TBNA. In our series, however, there was no difference in the yield among CDP with respect to location of the lesion in the upper lobes. The addition of TBNA, on the other hand, significantly increased the diagnostic yield from these areas, as well as from other lobes. No significant complications, either related to the procedure or to bronchoscopic damage, were observed with the use of TBNA. TBNA was exclusively diagnostic in 20% of patients, such that overall diagnostic yield was increased from 76 to 96%, and subset yields from 84 to 97% in EML, and from 65 to 96% in SPD. This has implications not only from a cost point of view, but 1240 Clinical Investigations

5 more importantly from the perspective of improving patient care by rendering earlier diagnosis and treatment plans and reducing the morbidity from subsequent repeat or new procedures needed to obtain final diagnosis. Based on the diagnostic yield obtained from this series, we conclude that TBNA is a safe procedure that should be routinely used to increase diagnostic yield in patients with EML or SPD. In patients with SPD, TBNA should be considered the procedure of choice. In EML, TBNA should be combined with EBB and BB to maximize yield, under which situation BW may be eliminated. Depending on the confidence level of the operator, BW may be collected and stored, and analyzed only if all other test results are negative. If lesions are deemed to be carcinoma in situ, TBNA may have limited value. References 1 Dasgupta A, Mehta AC, Wang KP. Transbronchial needle aspiration. Semin Respir Crit Care Med 1997; 18: Shure D, Fedullo PF. Transbronchial needle aspiration of peripheral masses. Am Rev Respir Dis 1983; 128: Zavala DC. Diagnostic fiberoptic bronchoscopy: techniques and results of biopsy in 600 patients. Chest 1975; 68: Shure D, Astarita RW. Bronchogenic carcinoma presenting as an endobronchial mass: optimal number of biopsy specimens for diagnosis. Chest 1983; 83: Popovich J, Kvale PA, Eichenhorn MS, et al. Diagnostic accuracy of multiple biopsies from flexible fiberoptic bronchoscopy. Am Rev Respir Dis 1982; 125: Shure D, Fedullo PF. Transbronchial needle aspiration in the diagnosis of submucosal and peribronchial bronchogenic carcinoma. Chest 1985; 88: Kvale PA, Bode FR, Kini S. Diagnostic accuracy in lung cancer: comparison of techniques used in association with flexible fiberoptic bronchoscopy. Chest 1976; 69: Buirski G, Calverley PMA, Douglas NJ, et al. Bronchial needle aspiration in the diagnosis of bronchial carcinoma. Thorax 1981; 36: Lundgreen R, Bligman F, Angstrom T. Comparison of transbronchial fine needle aspiration biopsy, aspiration of bronchial secretion, bronchial washing, brush biopsy and forceps biopsy in the diagnosis of lung cancer. Eur J Respir Dis 1983; 64: Bilaceroglu S, Gunel O, Cagirici U, et al. Comparison of endobronchial needle aspiration with forceps and brush biopsy in the diagnosis of endobronchial lung cancer. Monaldi Arch Chest Dis 1997; 52: Mehta AC, Ahmad M, Nunez C, et al. Newer procedures using the fiberoptic bronchoscope in the diagnosis of lung cancer. Cleve Clin J Med 1987; 54: Solomon DA, Solliday NH, Gracey DR. Cytology in fiberoptic bronchoscopy: comparison of bronchial brushing, washing and post-bronchoscopy sputum. Chest 1974; 65: Jones DF, Chin R Jr, Cappellari JO, et al. Endobronchial needle aspiration in the diagnosis of small-cell carcinoma. Chest 1994; 105: CHEST / 115 / 5/ MAY,