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Interact CardioVasc Thorac Surg 2009;9:232-235. doi:10.1510/icvts.2009.204263 © 2009 European Association of Cardio-Thoracic Surgery
Endobronchial ultrasound-guided transbronchial needle aspiration of undiagnosed intrathoracic lesions
a Department of Cardiothoracic Surgery, Odense University Hospital, Sdr. Boulevard 29, Odense, DK-5000, Denmark Received 2 February 2009; received in revised form 19 April 2009; accepted 30 April 2009
*Corresponding author. Tel.: +45 66144103; fax: +45 65916935.
Endobronchial ultrasound-guided transbronchial fine-needle aspiration (EBUS-FNA) is a minimally invasive method used routinely for mediastinal staging of patients with lung cancer. We have used it in 135 consecutive patients with a radiologically suspicious intrathoracic lesion that remained undiagnosed despite bronchoscopy and CT-guided fine-needle aspiration (CT-FNA). There was no operative mortality or surgical complications. In 98 patients with a suspicious lesion in the lung parenchyma, adequate tissue was obtained in 83 patients (85%) and in 37 patients with enlarged lymph nodes or a mediastinal tumor adequate tissue was obtained in 35 cases (95%). However, a final diagnosis was only reached in 45% of the patients and further investigations led to malignancy in 13. We believe that EBUS-FNA represents a good alternative to more invasive diagnostic procedures when conventional methods fail, even though the diagnostic yield is lower compared with mediastinal staging in patients with known lung cancer. In almost half of the cases, EBUS-FNA provides the final diagnosis without exposing the patient to the risk of complications from more invasive procedures.
Key Words: Lung cancer; Mediastinum; Diagnostics; Staging; EBUS
Radiologically suspicious lesions in the chest may represent lung cancer and warrants further workup. In order to guide correct therapy it is important to establish a diagnosis which is commonly achieved by conventional bronchoscopy or CT-guided fine-needle aspiration (CT-FNA). Bronchoscopy has a diagnostic yield of 20–60% [1, 2]. CT-FNA has a pooled sensitivity of 90% for peripheral lesions [2] and 83% for mediastinal masses [3]. Thus, a number of patients remain undiagnosed despite these common investigations. The next step to get a tissue diagnosis is often repeating the bronchoscopy/CT-FNA or performing a mediastinoscopy which is an invasive surgical procedure that poses a small but significant risk to the patient [4]. Less invasive methods have emerged including blind transbronchial needle aspiration (TBNA), endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), and most recently endobronchial ultrasound-guided transbronchial fine-needle aspiration (EBUS-TBNA). Even though mediastinoscopy is considered the gold standard for mediastinal staging of lung cancer [5] EBUS-TBNA is also a well established method for this indication [5–9]. Other investigators have demonstrated that EBUS-TBNA may also be used in the diagnostic workup of patients with suspicious central masses [10, 11], but these were smaller series and just for centrally located intrathoracic lesions. Although the echo image in EBUS may give a clue to whether a suspicious lesion is malignant or not [12], it is of paramount importance to obtain material for cytological or histological diagnosis. The aim of this study was to assess the value of EBUS-TBNA in the further diagnostic workup of patients who remained undiagnosed following conventional investigations.
During a 24-month period (January 2006 to December 2007), 292 patients underwent EBUS-TBNA at our institution. One hundred and fifty-seven (157) patients (54%) had an established diagnosis of lung cancer and were referred to us for mediastinal staging. The remaining 135 patients (46%) had a radiologically suspicious lesion in the lung parenchyma (n=98), enlarged lymph nodes in the mediastinum (n=27), a suspicious tumor in the mediastinum (n=6) or rare causes (n=4) as demonstrated in Fig. 1. In this retrospective study, all 135 patients had a previous chest CT and bronchoscopy including brush cytology but remained undiagnosed. In addition, 15 patients with a peri- pheral parenchymal lesion also underwent CT-FNA without getting a tissue diagnosis.
All EBUS-TBNA examinations were performed in general anesthesia with a linear scanner (BF-UC160F, Olympus). Masses in the mediastinum, lung parenchyma or enlarged paratracheal or hilar lymph node stations 2, 3, 4, 7, 10 and 11 according to Mountain et al. [13], were systematically identified and punctured. Fine-needle aspiration was performed with a 22G needle (NA-201SX-4022, Olympus) during real-time EBUS. Two aspirations were performed from each lesion to ensure that the biopsy contained sufficient material. Aspirated material was expelled onto glass slides and smeared for cytological examination or expelled into saline for preparation of cell blocs for histological examination. Rapid on-site evaluation was not performed. Instead, all biopsies were reviewed the following day by an experienced pathologist, and classified as ‘malignant’, ‘benign’ or ‘nondiagnostic’ as shown in Fig. 2. The latter group was further subdivided into biopsies with adequate cell sample (presence of lymphocytes) or inadequate cell sample without lymphatic tissue. All but three patients with inadequate samples were referred for more invasive methods including mediastinoscopy (n=7), thoracoscopy (n=3), thoracotomy (n=3) or re-broncoscopy (n=1). The last three patients with inadequate diagnostic material were followed in the outpatient clinic because chest-CT demonstrated regression of the lesion. Patients with adequate cell samples were also followed in outpatient clinics and were subsequently referred for more invasive procedures if their chest-CT showed progression of the tumor.
The median age of the 135 patients with an undiagnosed radiologically suspicious lesion was 67 years (range 29–86 years) and 76 were men (56%). There was no operative mortality or any surgical complications. All patients were discharged from the hospital on the day of surgery. In 98 patients with a suspicious lesion in the lung parenchyma, adequate samples were obtained in 83 patients (85%), and in 37 patients with enlarged lymph nodes or a mediastinal tumor adequate samples were obtained in 35 cases (95%). The location and pathology of the lesions are presented in Fig. 1. However, diagnostic yield (defined as samples with definite malignant or benign pathology) was 45%. During the first year (2006) the diagnostic yield was 51% and the number of biopsies with inadequate diagnostic material was 18%. In the second year (2007) these numbers were 38% and 5%, respectively. As demonstrated in Fig. 1, EBUS-TBNA could not provide a final diagnosis in 74 patients (55%). Some patients (n=21) were later diagnosed after further investigations: Nine patients had NSCLC diagnosed at thoracotomy (n=4), re-EBUS-FNA (n=1), re-broncoscopy (n=1), mediastinoscopy (n=2) and the last patient by CT-FNA. Thoracoscopy with pleural biopsy demonstrated mesothelioma in one patient, mediastinoscopy revealed B-cell lymphoma in another patient and two patients were diagnosed with pulmonary metastases from other malignancies at thoracotomy. In the last eight patients a benign diagnosis was obtained at thoracotomy (n=5), thoracoscopy (n=1), re-broncoscopy (n=1) or mediastinoscopy (n=1). The final pathological diagnoses are shown in Fig. 2.
Patients with a radiologically suspicious tumor in the lung parenchyma or the mediastinum, who remain undiagnosed after conventional diagnostic evaluation by bronchoscopy and/or CT-guided biopsy, pose a challenge to the clinician. Typically, such patients are referred for more invasive procedures such as mediastinoscopy, thoracoscopy or even thoracotomy, but these invasive procedures all carry a small but definite risk to the patient, and they are costly. EBUS-TBNA is a relatively new diagnostic modality which is less invasive and more cost-effective because it allows investigation in an outpatient setting. We have used EBUS routinely for three years. Mediastinal staging remains the primary indication but the number of patients without a definite diagnosis despite conventional investigations by bronchoscopy or CT-FNA continues to rise. The present study demonstrates that in approximately 45% of such patients a valid diagnosis can be reached minimally invasive by EBUS-TBNA. This diagnostic yield is lower than yields commonly reported following mediastinal staging of patients with known lung cancer [5, 8] but it is important to distinguish the two patient populations. Inevitably, the present patient population is selected and thus biased because conventional diagnostic methods failed to give a diagnosis. It is likely that EBUS used as the primary diagnostic modality would increase the chance of reaching a valid diagnosis. Other investigators have used EBUS to provide the primary diagnosis of centrally located suspicious masses with high degree of success [11]. Another study concluded that EBUS-TBNA for primary diagnosis was superior to transbronchial biopsy in peripheral lung lesions smaller than 3 cm [7]. One may argue that we did not select patients properly for EBUS and that in some patients it would be virtually imposible to achieve a diagnosis by EBUS. However, we only considered patients for EBUS if we were convinced that we had a fair chance of getting an adequate tissue sample from either the tumor or enlarged lymph nodes. It may also be argued that we simply were not experienced enough and that our results reflect our learning curve. However, our team was not inexperienced and during the same period we performed EBUS for mediastinal staging of lung cancer with a sensitivity of 85% in 157 patients [14]. Furthermore, previous investigators who focused on the learning curve in EBUS concluded that the number of investigations necessary to become experienced was just 10 procedures [15]. In addition, all EBUS examinations were performed in general anesthesia which is likely to allow a more thorough examination of the patient and consequently increase the diagnostic yield. We appreciate that EBUS may be used under local anesthesia, but we fear that patient compliance is lower. Finally, our results demonstrate that the diagnostic yield was higher in the first year of the study period compared with the second year, which contradicts speculations of a learning curve. The lower diagnostic yield in the last part of the study period may be explained by a team performing EBUS-TBNA on a wider indication but this is purely speculative. The diagnostic yield in EBUS-TBNA and other techniques depends on the location of the lesion and is higher in central than peripheral tumors [2]. As demonstrated in Fig. 1, our results confirm these findings because a final diagnosis was reached in 60% of patients with a central lesion but only in 32% of peripheral lesions. However, the number of adequate tissue samples was similar irrespective of location, demonstrating that EBUS-TBNA may indeed contribute in the diagnostic workup of peripheral lesions. The lower diagnostic yield in peripheral lesions may be explained by interposition of aerated lung tissue which disturbs the ultrasound image when targeting the actual peripheral lesion, as well as dependency of malignant cells in the hilar lymph nodes if one cannot actually puncture the peripheral lesion. In conclusion, we believe that EBUS-TBNA represents a fine alternative to more invasive diagnostic procedures when conventional methods fail to give the diagnosis in radiologically suspicious lesions. In almost half of such patients this minimally invasive diagnostic modality provides a final diagnosis without exposing the patient to the risk of complications from more invasive procedures [4, 15]. However, EBUS-TBNA does not replace more invasive methods. It is also important to emphasize that the diagnostic yield of EBUS-TBNA in patients without a definite diagnosis after conventional diagnostic investigation is lower compared with the diagnostic yield in patients with known lung cancer, who are referred for mediastinal staging of and that many undiagnosed patients will need more invasive workup.
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Abstract
1. Introduction
