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* From the Columbia University Medical Center (Dr. Patel), New York, NY; and The University of Chicago (Ms. Pohlman, and Drs. Husain, Noth, Hall, and Kress), Chicago, IL.
Correspondence to: Nina M. Patel, MD, Columbia University, Medicine, Division of Pulmonary & Critical Care, 622 W 168th St, PH 8 East, Room 840, New York, NY 10032; e-mail: np2199{at}columbia.edu
Abstract
Background: Previous studies have suggested a decreased need for the surgical biopsy of intrathoracic lymph nodes (LNs) due to improved diagnostic rates utilizing transbronchial needle aspiration (TBNA) with endobronchial ultrasound and endoscopic ultrasound. The goal of this study was to determine whether conventional TBNA using combined cytologic and histologic analysis of tissue specimens impacted the rates of surgical diagnostic biopsies of patients with intrathoracic lymphadenopathy.
Methods: Retrospective review at a single academic center. All mediastinal and hilar tissue samples submitted for pathologic analysis over an 8.4-year period were analyzed. Patients were categorized into a "before" group and an "after" group based on two different time periods. The before group underwent only cytologic analysis of Wang needle (19-gauge or 21-gauge) aspirates. The after group had cytologic analysis of aspirates as well as histologic analysis of needle "core" (19 gauge) biopsy specimens. The groups were compared for the rate of intrathoracic LNs sampled by surgical means vs TBNA and the number of times that TBNA averted the need for a surgical diagnostic procedure.
Results: The success of TBNA increased significantly in the after group compared to that in the before group. The yield for the successful sampling of mediastinal and hilar LNs increased from 53 to 91% (p < 0.001) in the before group vs the after group. TBNA averted a surgical biopsy in 35% of the before cases compared to 66% of the after cases (p < 0.001).
Conclusions: Conventional TBNA using large-bore needles with both cytology and surgical pathology evaluation decreases the need for surgical sampling of the mediastinum to diagnose thoracic lymphadenopathy.
Key Words: core needle biopsy • endobronchial ultrasound • endoscopic ultrasound • mediastinoscopy • transbronchial needle aspiration
The importance of transbronchial needle aspiration (TBNA) as a tool for diagnosing intrathoracic lymphadenopathy as well as in the staging of lung cancer has been validated in a number of studies.1234 To date, however, surgical procedures (eg, mediastinoscopy, mediastinotomy, thoracotomy, and video-assisted thoracoscopy) have been the methods of choice for definitive sampling of mediastinal and hilar tissue. For example, guidelines5 have suggested that in patients with non-small cell lung cancer in whom curative surgical resection is a possibility, mediastinoscopy is the sampling procedure of choice. However, mediastinoscopy requires general anesthesia, and has been cited to have a 2 to 3% complication rate.6 In comparison, the complication rate for TBNA is < 1%.7 Furthermore, conventional mediastinoscopy cannot sample hilar tissue and is limited in the number of mediastinal lymph node (LN) stations that can be sampled.
Advances in TBNA techniques, including rapid on-site cytologic evaluation, the use of 19-gauge needles for performing core biopsies, and, more recently, endoscopic and endobronchial ultrasound (EBUS) guidance have increased the diagnostic yield of this procedure considerably.28910111213 In a randomized trial of 200 patients comparing conventional TBNA to EBUS-guided TBNA, Herth et al11 demonstrated an overall diagnostic yield of 80% utilizing EBUS-guided TBNA vs 71% (p < 0.05) utilizing conventional TBNA. However, EBUS-guided TBNA requires sophisticated, costly equipment and extensive operator training. As a result, the current application of EBUS-guided TBNA is limited to select centers and likely will not have extensive availability. In contrast, conventional TBNA is a technique that has the potential for widespread use since no sophisticated or costly equipment is necessary. To date, EBUS-guided TBNA has been reported814 to reduce the need for mediastinoscopy; however, there are limited data reporting the impact of conventional TBNA on the surgical sampling of intrathoracic lymph tissue.
We modified the approach to conventional TBNA at our institution in an effort to improve our success with this technique. We changed from a strategy of specimen submission to the cytopathology department alone to one in which needle core biopsy specimens were submitted to our surgical pathology department in addition to being sent for cytopathologic analysis. The goals of this study were to evaluate the impact of this change on the diagnostic yield of TBNA, as well as the impact of conventional TBNA, using this combined pathologic evaluation on the need for surgical sampling of intrathoracic LNs.
Materials and Methods
We performed a retrospective review of all mediastinal and hilar tissue samples submitted for pathologic analysis at our institution over an 8.4-year period (January 1, 1997, to May 15, 2005). The study was approved by the institutional review board at the University of Chicago with a waiver of consent since the study involved an anonymous, retrospective evaluation of medical records only. One thousand six hundred six billing records were queried for all patients who underwent bronchoscopy with TBNA. In addition, 2,848 pathology records were queried for the following terms: "mediastinum"; "Wang"; "transbronchial needle aspiration"; "lymph node"; and "mediastinoscopy." These two databases were merged to yield a total of 2,543 patients, which included all patients who had intrathoracic LNs sampled by bronchoscopic and surgical approaches. Because endoscopic ultrasound (EUS) and CT scan-guided biopsies accounted for a very small fraction of the intrathoracic LNs sampled (< 3%), they were not included in the analysis. The age, gender, procedure date, mediastinal/hilar sampling approach, LN stations biopsied, and biopsy results were recorded for all patients. Biopsy results were categorized as follows: (1) malignant; (2) benign pathology (eg, granuloma); (3) normal lymphoid tissue; and (4) nondiagnostic (eg, no tissue/cells, blood only, or bronchial mucosa cells only). Intrathoracic LN sampling success was defined a priori as successful sampling of any mediastinal or hilar tissue (malignant pathology, benign pathology [eg, granuloma], or normal lymphoid tissue).
Beginning on December 1, 2003, the approach to TBNA was systematically changed at our institution. Before this time, TBNA procedures were performed using either a 19-gauge or a 21-gauge needle (BARD-Wang; Billerica, MA), and all aspirates were either smeared directly onto slides and sprayed with cytology fixative or were injected into a preservative solution (Cytolyt; Cytyc Corp; Boxborough, MA). Cytologic analysis alone was performed. Starting on December 1, 2003, all TBNA procedures were performed using 19-gauge needles only (BARD-Wang). All samples were injected into the preservative solution (Cytolyt; Cytyc Corp), and subsequently were strained through lens paper and submitted in toto for formalin fixation followed by paraffin embedding. The core biopsy fragments were processed by our surgical pathology department. Cell blocks were sliced at levels 1, 5, and 10, and were stained with hematoxylin-eosin for histologic analysis (Fig 1, 2 ). The remaining fluid and aspirate samples were sent to our cytopathology department for cytologic analysis (Fig 3 ). Based on this systematic change to the approach to TBNA, the database was divided into a "before" group (prior to December 1, 2003) and an "after" group (from December 1, 2003 to May 15, 2005). Bronchoscopists experienced in TBNA performed bronchoscopies in all cases. In the before period, there were 10 bronchoscopists, while in the after period there were 9 bronchoscopists. Seven bronchoscopists covered both periods.
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For those patients whose TBNA biopsy specimens showed normal lymphoid tissue only, clinical courses were assessed through the utilization of retrospective chart review for a minimum follow-up period of 9 months. Outcomes in these patients were discerned through findings on surgical or radiology-assisted biopsy and/or through stability on imaging studies (eg, LNs of same size or decreased size over time, positron emission tomography [PET] scans and/or CT scans) in conjunction with a stable clinical course. TBNA was considered to have averted a surgical biopsy if the biopsy results showed either (1) definitive benign pathology or (2) malignant pathology with clinical staging sufficient to preclude the need for subsequent diagnostic surgical intervention.
Statistical Analysis
Continuous data from the two time periods were compared using a t test (parametric) or a Mann-Whitney U test (nonparametric) as appropriate. Categoric data were compared using the 
2 test or Fisher exact test, as appropriate. For the four end points listed above, the before and after groups were compared using 2 analysis with Yates correction.
Results
Two hundred seventeen patients underwent TBNA of enlarged mediastinal or hilar LNs (before group, 75 patients; after group, 142 patients). Seven hundred ninety-nine patients underwent surgical sampling of intrathoracic lymphadenopathy during the same time period (before period, 644 patients; after period, 155 patients). There was no significant gender difference between the before and after groups for TBNA or mediastinoscopy (Table 1 ). The TBNA after group was significantly older than the before group (mean age, 62 vs 56 years, respectively; p < 0.001). The incidence of lung cancer was not different between the before and after groups (59% vs 61%, respectively; p = 0.23). We encountered no significant complications (eg, hemorrhage requiring hospital or ICU admission, or transfusion, endotracheal intubation, surgical intervention, respiratory failure, or death).
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In our study, we examined the diagnostic yield of conventional TBNA in mediastinal and hilar LN sampling. Our approach did not rely on more complicated algorithms such as rapid on-site cytologic evaluation or EBUS. Our success rate in sampling mediastinal or hilar tissue (normal and abnormal) in the after group was 91%. We achieved this rate using 19-gauge Wang needles with combined cytologic and histologic analysis of TBNA specimens. As Figures 1and 2 reveal, using histologic analysis can provide sizeable biopsy specimens, with preserved architecture, for analysis. Others have demonstrated similar findings. Schenck et al2 demonstrated an 87.5% success rate for sampling mediastinal tissue in a series of 64 patients; Hermens et al15 and Cetinkaya et al16 revealed a 79% success rate in sampling mediastinal tissue using histologic and cytologic analysis, respectively. However, our findings demonstrated equal or greater success in sampling hilar lymphadenopathy without the use of EBUS, compared to subcarinal or paratracheal lymphadenopathy.3411 In sum, we established that the diagnostic yield of TBNA is excellent using a simple, easily applicable, inexpensive technique.
Our modification of the approach to the conventional TBNA procedure and tissue analysis had a significant impact on the need for the surgical biopsy of intrathoracic LNs, a finding that has not been described previously. Surgery was avoided almost twice as often in patients from the after group (66% of the time overall, compared to 34% of patients from the before group). Previous studies415 also have suggested that conventional TBNA may preclude unnecessary mediastinoscopies. Sharafkhaneh et al4 studied a series of 166 patients and found that 15 of 25 patients with subcarinal lymphadenopathy positive for malignancy by TBNA did not proceed to a surgical procedure for diagnosis. Hermens et al15 avoided 10 mediastinoscopies in a series of 106 patients who underwent diagnostic TBNA. To our knowledge, however, these studies did not systematically review institutional practice comparing overall rates of surgical sampling of intrathoracic lymphadenopathy to those of TBNA sampling. Also, these studies did not review as large a patient population as is presented in the current study.
More recent literature91214 also suggests a decreased need for surgical biopsy of intrathoracic lymphadenopathy with the advent of endoscopically guided TBNA. In a prospective evaluation of 105 patients with enlarged (ie, > 1 cm on CT scan) mediastinal or hilar lymphadenopathy, Yasufuku et al8 concluded that 41 surgical procedures were avoided through the diagnostic results of EBUS-guided TBNA. Numerous previous studies9121417 examining esophagraphic ultrasound-guided fine-needle aspiration (ie, EUS) of intrathoracic lymphadenopathy have concluded that EUS-fine-needle aspiration decreased the need for mediastinoscopy. The major limitation to endoscopic and EBUS-guided TBNA, however, is that extensive operator training may be necessary to yield the diagnostic accuracies seen in the aforementioned studies. At present, EBUS-guided TBNA is not readily available at many institutions. Since our approach to TBNA requires no special equipment, it has the potential for widespread adaptation and utilization.
There are several limitations to our study. First, our study does not take into account the average size of LNs sampled by TBNA. It is possible that the increased diagnostic yield we observed was impacted by larger LN size in the after group. We think this is unlikely as our threshold for sampling intrathoracic LNs (> 1 cm on CT) was not altered throughout the study period, and the incidence of lung cancer was the same between the two periods. Second, although our operators were largely the same between the two periods, previous data indicate that increasing operator experience in and of itself can increase the diagnostic yield of TBNA.1819 As such, it is possible that the increased diagnostic yield was partially imparted by more experienced operators. Also, PET scanning was introduced during the study period. It is possible that this modality may have had an impact on rates of surgical sampling. Twenty-eight percent of patients in the after group had positive PET scan findings, and < 2% of patients in the before group had positive PET scan findings. Additionally, it is possible that clinicians came to view TBNA with a greater comfort level during the study period, thereby impacting the subsequent workup of adenopathy. Last, one quarter of patients who had "normal lymphocytes" on TBNA proved ultimately to have malignancy on surgical biopsy specimens. Clearly, TBNA results showing normal lymphoid tissue do not definitively rule out malignant disease. It is conceivable, as well, that some patients with stable lymphadenopathy over months actually had a slow-growing cancer rather than a benign diagnosis. In our study, of the 39 patients with normal lymphoid tissue on TBNA samples in the after group, 18 were ultimately found to have normal lymphoid tissue by alternate means. As such, in those patients who have a normal TBNA result, clinical context should be taken into account regarding decisions to pursue more aggressive surgical biopsies. It is noteworthy that the majority of patients with normal lymphoid tissue on TBNA did not have malignant disease. However, a patient whose TBNA result showed normal lymphoid tissue only must undergo careful and frequent clinical follow-ups. The decision to proceed to a surgical biopsy vs ongoing observation and imaging studies should be evaluated on a case-by-case basis.
Our data support the notion that conventional TBNA is a reasonable initial step in the evaluation of intrathoracic lymphadenopathy. In approximately two thirds of patients, no further diagnostic testing will be necessary following a TBNA procedure. Further prospective studies of conventional TBNA are needed to corroborate these findings. In conclusion, we have demonstrated that conventional TBNA using a large-bore needle with both cytopathologic and surgical histopathologic evaluations appears to decrease the need for surgical sampling of intrathoracic lymphadenopathy. This approach should be considered as an initial step in the evaluation of patients with undiagnosed mediastinal and hilar adenopathy.
Footnotes
Abbreviations: EBUS = endobronchial ultrasound; EUS = endoscopic ultrasound; LN = lymph node; PET = positron emission tomography; TBNA = transbronchial needle aspiration
The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.
Received for publication May 31, 2006. Accepted for publication September 26, 2006.
References
This article has been cited by other articles:
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  G. Stratakos, I. Porfyridis, V. Papas, C. Kandaraki, C. Zisis, V. Mariatou, A. Liapikou, C. Roussos, and S. Zakynthinos Exclusive Diagnostic Contribution of the Histology Specimens Obtained by 19-Gauge Transbronchial Aspiration Needle in Suspected Malignant Intrathoracic Lymphadenopathy Chest, January 1, 2008; 133(1): 131 - 136. [Abstract] [Full Text] [PDF]
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