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Mediastinal Lymphadenopathy: Diagnostic Yield of Transbronchial Mediastinal Lymph Node Biopsy with CT Fluoroscopic Guidance-Initial Experience¹

¹ From the Departments of Radiology (S.N.G., V.R., P.M.B., K.J.E.) and Interventional Pulmonology (A.E.), Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215. Received October 14, 1999; revision requested November 16; revision received December 16; accepted December 21. Address correspondence to S.N.G. (e-mail: sgoldber@caregroup.harvard.edu).

	ABSTRACT

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
PURPOSE: To determine whether the use of computed tomographic (CT) fluoroscopy to guide transbronchial needle aspiration (TBNA) of mediastinal lymph nodes can improve the diagnostic yield.

MATERIALS AND METHODS: CT fluoroscopy was used to guide TBNA in 12 consecutive patients with mediastinal lymphadenopathy who had previously undergone nondiagnostic conventional TBNA. CT fluoroscopy was used to confirm the location of the biopsy needle by using a "quick-check" technique (ie, fluoroscopy was performed sparingly after needle insertion). The location of each needle, the total procedural and fluoroscopic times, and any complications were recorded.

RESULTS: All CT fluoroscopic procedures were performed in less than 1 hour, and a tissue diagnosis was established in all patients. Eighteen lymph nodes with a diameter of 0.8–2.4 cm were sampled with 116 needle passes. CT fluoroscopy documented inadequate positioning in 48 of the 116 (41.3%) needle passes. Eighteen (15.5%) needles did not fully penetrate the tracheobronchial tree. Six needles (5.2%) were placed into the great vessels. Malignant disease was diagnosed in nine patients, and benign disease was diagnosed in three. The mean fluoroscopic exposure time was 20.5 seconds ± 12.7. No pneumothoraces or substantial hemorrhage were observed.

CONCLUSION: CT fluoroscopic guidance for TBNA procedures is a safe and efficient means of providing diagnostic material and should be considered for patients who have previously undergone nondiagnostic blinded TBNA.

Index terms: Computed tomography (CT), guidance, 679.12111, 679.1262 • Lymphatic system, biopsy, 679.1262 • Lymphatic system, CT, 679.12111 • Lymphatic system, diseases, 679.3159, 679.321, 679.33, 679.34

	INTRODUCTION

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
The diagnosis and staging of intrathoracic disease often requires a tissue diagnosis from lymph nodes adjacent to the tracheobronchial tree. Currently, flexible bronchoscopy with transbronchial needle aspiration (TBNA) is the least invasive method for sampling tissue in this region (1–7). Because there are few landmarks within the intraluminal tracheobronchial tree, however, the diagnostic yield for conventional flexible bronchoscopy has been variable, with the rate of unsuccessful biopsy reported to be 10%–66% (1–8). Thus, more invasive procedures (ie, mediastinoscopy or open biopsy) are often necessary to obtain a tissue diagnosis following unsuccessful attempts at TBNA (1).

Computed tomography (CT) has been demonstrated to be reliable for helping guide percutaneous biopsy and confirm optimal needle positioning within pulmonary and mediastinal lesions (9,10). Rong and Cui (11) have reported the use of conventional CT guidance to help improve the yield of TBNA. This practice, however, has not been widely adopted given the impracticality of an interrupted scanning technique with repeated irradiation of the bronchoscopist, who must maintain delicate and proper needle positioning during scanning. Recently, CT fluoroscopic techniques have been developed that reduce the time necessary to perform CT-guided biopsy and enable the acquisition of images while the operators are in the CT suite (12–14). Thus, this technique has been shown to be feasible for directing fine-needle aspiration with flexible bronchoscopy (15). We performed this study to determine whether the addition of CT fluoroscopy to guide flexible bronchoscopic biopsy can help improve the diagnostic yield in patients who had previously undergone nondiagnostic TBNA biopsy with conventional flexible bronchoscopy but no additional imaging guidance.

	MATERIALS AND METHODS

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Demographics
Twelve consecutive patients in whom mediastinal lymphadenopathy was documented at CT underwent TBNA with CT fluoroscopic guidance between December 13, 1998, and April 14, 1999. The subcarinal and paratracheal lymph nodes in these patients had a short-axis dimension of 0.8–2.4 cm (mean ± SD, 1.5 cm ± 0.5) at CT and a high pretest probability of malignancy. The mean patient age was 64.4 years (range, 31–86 years). There were eight men and four women. All patients had previously undergone nondiagnostic conventional (ie, without CT fluoroscopic guidance) TBNA, which was performed by experienced interventional pulmonologists after review of all imaging findings with a board-certified radiologist. The CT fluoroscopy–guided procedure was performed within 3 weeks of conventional TBNA in 11 (92%) patients and 11 weeks after conventional TBNA in one (8%) patient. Consultation with members of our institutional review board indicated that formal approval for this study was not necessary. Informed consent was obtained from all patients at enrollment.

Procedural Technique
Procedures were performed with a CT unit (Somatom Plus 4; Siemens, Erlangen, Germany). The patients underwent intravenous administration of 1–2 mg midazolam and 50–150 µg fentanyl citrate for conscious sedation. Transverse nonenhanced CT scans were obtained through the region of interest to confirm the exact location for biopsy. These images also showed that the short-axis diameter of the targeted lesion did not increase by more than 2 mm during the interval between the conventional and imaging-guided TBNA procedures. The level of the lymph nodes to be sampled was marked on the patients’ skin to serve as an external anatomic reference.

Bronchoscopy
TBNA was performed by an interventional pulmonologist (A.E.) whose experience with these techniques (6 years) was comparable to that of the referring clinicians. All patients received nothing by mouth after midnight before bronchoscopy. Standard monitoring was performed with continuous oximetric, blood pressure, and pulse measurements. After topical anesthesia was achieved with nebulized 2% lidocaine hydrochloride and 20% benzocaine, the flexible bronchoscope (Olympus America, Melville, NY) was introduced transnasally or transorally. After visualization of the vocal cords, additional topical anesthetics were applied as needed. TBNA was performed in a conventional fashion (16), as outlined subsequently.

Before the biopsy needle was inserted, the initial CT scans were reviewed by the radiologist and the interventional pulmonologist to determine the most suitable location for needle insertion. A 22-gauge cytology needle (MW 122; Mill-Rose Laboratories, Mentor, Ohio) was placed via the working channel of the bronchoscope and inserted transbronchially by using a jabbing motion. A 60-mL syringe attached to the end of the catheter was then used to apply suction while the needle was agitated to collect cellular material. After TBNA was performed, the endobronchial tree was carefully inspected and, if indicated, endobronchial samples were obtained.

CT Fluoroscopy
CT fluoroscopy (50 mA, 120 kVp, 0.25-second acquisition time, 10-mm section thickness) was performed to help confirm the location of the transbronchial biopsy needle. Despite the potential for real-time visualization of needle placement with CT fluoroscopy, we were unable to document the placement of the needle in real time owing to scatter artifact from the thick metallic bronchoscope. In addition, we found it difficult to identify readily and accurately the free needle tip within the airway before its insertion into mediastinal structures that had soft-tissue attenuation. Thus, a "quick-check" technique (ie, use of fluoroscopy sparingly after needle insertion) was used in an effort to reduce the overall radiation exposure (14). The location of each needle, the number of needle passes, and the total CT fluoroscopic time were recorded. A final CT fluoroscopic image was obtained to document the presence of pneumothorax or hemorrhage.

Histopathologic Analysis
Once removed with the bronchoscope, the aspirated material was smeared immediately on glass slides, and the needle was washed in Cyto-lyte medium (Cytech, Boxboro, Mass). On-site rapid cytologic analysis was performed by certified cytologic technologists to confirm that an adequate sample was collected. A diagnosis of malignant disease was based on results of histopathologic analysis of specimens by board-certified pathologists. A diagnosis of benign disease was based on results of histopathologic analysis and clinical and imaging follow-up.

	RESULTS

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All procedures yielded diagnostic material and were performed in 1 hour or less (range, 30–60 minutes), a procedure length similar to that of conventional non–image-guided TBNA at our institution. Samples were obtained from 18 lymph nodes (seven subcarinal and 11 paratracheal) with a diameter of 0.8–2.4 cm. Three to 10 (mean ± SD, 6.3 ± 2.2) needle passes were attempted in each lymph node to ensure that a minimum of three samples were obtained. The number of passes performed with this technique is similar to that for conventional non–image-guided TBNA at our institution. A total of 116 passes were performed in the 18 sampled nodes.

Direct visualization of the tracheobronchial tree failed to identify a deformity or other anatomic landmarks (other than the carina) to help guide the placement of the biopsy needle. Thus, from a bronchoscopic perspective, the needle was inserted in a blinded fashion.

With proper CT section selection (achieved by manually adjusting the anatomic level at which the patient was scanned), the needle tip was well visualized as a thin area of high attenuation with a distinctly metallic appearance (Fig 1). CT fluoroscopy helped confirm that only six (33%) of the 18 initial needle passes were adequately positioned within the lymph node target. Further needle passes, together with bronchoscopic visualization of the initial needle insertion site as an anatomic landmark to guide subsequent insertions, were directed with CT fluoroscopy to document the needle location in relation to the target. This increased the rate of successful node targeting for later needle passes to 62% (60 of 96 passes). In addition, CT fluoroscopy was further able to help confirm sampling within multiple representative regions throughout the lymph node.

View larger version (90K): [in this window] [in a new window] [Download PPT slide]   Figure 1. TBNA with CT fluoroscopic guidance. Transverse CT fluoroscopic image shows a thin biopsy needle (straight solid arrow) in a 0.8-cm-diameter right paratracheal lymph node (open arrow). The needle can be differentiated from the thicker needle sheath (curved arrow), which remains within the trachea. The needle tip is within 3.0 mm of the superior vena cava (S). Non-small cell lung cancer was diagnosed with this technique.

View larger version (86K): [in this window] [in a new window] [Download PPT slide]   Figure 2a. TBNA with CT fluoroscopic guidance. (a) Subserosal needle insertion. Transverse CT fluoroscopic image shows that the tip of the biopsy needle intersects the plane of the tracheal wall and is not well centered in the 1.8-cm-diameter paratracheal lymph node (L). In addition, a portion of the needle (arrow) extends into the trachea. At histopathologic examination, only bronchial epithelial cells were obtained. (b) Transverse CT fluoroscopic image obtained after the needle was repositioned shows the needle tip (arrow) centered within the node. Lymphoma was diagnosed with the tissue sample obtained with this needle pass.

View larger version (96K): [in this window] [in a new window] [Download PPT slide]   Figure 2b. TBNA with CT fluoroscopic guidance. (a) Subserosal needle insertion. Transverse CT fluoroscopic image shows that the tip of the biopsy needle intersects the plane of the tracheal wall and is not well centered in the 1.8-cm-diameter paratracheal lymph node (L). In addition, a portion of the needle (arrow) extends into the trachea. At histopathologic examination, only bronchial epithelial cells were obtained. (b) Transverse CT fluoroscopic image obtained after the needle was repositioned shows the needle tip (arrow) centered within the node. Lymphoma was diagnosed with the tissue sample obtained with this needle pass.

View larger version (106K): [in this window] [in a new window] [Download PPT slide]   Figure 3a. Malpositioned needle placement within great vessels. (a) Transverse CT fluoroscopic image shows the tip of the biopsy needle (arrow) within the ascending aorta (Ao). (b) Transverse CT fluoroscopic image shows the needle tip (arrow) in the left atrium (LA). The needle traversed a 1.2-cm-diameter subcarinal lymph node. (c) Transverse CT fluoroscopic image demonstrates the needle within the right interlobar pulmonary artery (small arrow). Note the substantial metallic streak artifact from the bronchoscope (large arrow) and the 2.3-cm-diameter mass (M) at the right lung base.

View larger version (111K): [in this window] [in a new window] [Download PPT slide]   Figure 3b. Malpositioned needle placement within great vessels. (a) Transverse CT fluoroscopic image shows the tip of the biopsy needle (arrow) within the ascending aorta (Ao). (b) Transverse CT fluoroscopic image shows the needle tip (arrow) in the left atrium (LA). The needle traversed a 1.2-cm-diameter subcarinal lymph node. (c) Transverse CT fluoroscopic image demonstrates the needle within the right interlobar pulmonary artery (small arrow). Note the substantial metallic streak artifact from the bronchoscope (large arrow) and the 2.3-cm-diameter mass (M) at the right lung base.

View larger version (103K): [in this window] [in a new window] [Download PPT slide]   Figure 3c. Malpositioned needle placement within great vessels. (a) Transverse CT fluoroscopic image shows the tip of the biopsy needle (arrow) within the ascending aorta (Ao). (b) Transverse CT fluoroscopic image shows the needle tip (arrow) in the left atrium (LA). The needle traversed a 1.2-cm-diameter subcarinal lymph node. (c) Transverse CT fluoroscopic image demonstrates the needle within the right interlobar pulmonary artery (small arrow). Note the substantial metallic streak artifact from the bronchoscope (large arrow) and the 2.3-cm-diameter mass (M) at the right lung base.

Malignant disease was diagnosed in nine patients. Six patients had nodal involvement from lung cancer, two patients had lymphoma, and one patient had metastases from adenocarcinoma. Benign disease was diagnosed in three patients, including one with sarcoidosis in whom noncaseating granulomas were identified at histopathologic examination. In the remaining two patients, numerous benign lymphocytes were obtained from the enlarged reactive nodes. For these two patients, the results of 6-month clinical and CT follow-up failed to demonstrate other indications of malignancy in one patient and showed regression of the lymphadenopathy in the other. In addition, CT demonstrated a decrease in lymph node size in one patient and stability in the other. Thus, fluoroscopic guidance helped establish a tissue diagnosis in all 12 (100%) patients.

	DISCUSSION

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
Transbronchial biopsy is widely accepted as a cost-effective alternative to mediastinoscopy in the evaluation of mediastinal lymph nodes and is associated with a low complication rate (1–8). This technique, however, is limited by variable sensitivity for the detection of malignant lymph nodes, with false-negative results reported in 10%–66% of cases (1–8). CT fluoroscopic guidance can be used to help determine a tissue diagnosis on the basis of mediastinal lymph nodes samples obtained with transbronchial biopsy techniques. In this study, we were able to determine a correct tissue diagnosis in 12 consecutive patients in whom nondiagnostic results had been obtained at conventional TBNA. Our results confirm how difficult it is to target lesions accurately without imaging guidance, and they demonstrate the potential to increase the diagnostic yield and certainty with CT fluoroscopic guidance.

In this study, we were able to confirm a high percentage (42.1%) of needle insertions outside of the intended lymph node target. Given that the bronchoscopic biopsies were performed by an experienced bronchoscopist who used an otherwise standard technique, our imaging findings may help explain the relatively low yield with the conventional blinded approach. In addition, we were able to document that 15.5% of needle insertions did not pierce the full thickness of the tracheobronchial tree but remained in a submucosal location. We suspect that this phenomenon was due in large part to the cartilaginous rings of the trachea, which deflected the biopsy needle off axis and along the serosal plane of the trachea.

A small but substantial number of needle insertions (5.2%) were placed in the great vessels. Our results suggest that this was likely not a rare occurrence during blinded TBNA biopsy. When documenting the inappropriate position of the needle, however, we were able to remove the needle without incurring additional trauma from vigorous aspiration.

Our results suggest that a similar transbronchial biopsy technique with CT fluoroscopic guidance may not only provide a tool for tissue diagnosis but also has the potential to serve as a minimally invasive strategy for tumor staging. Currently, mediastinoscopy is often necessary to document positive N2 or N3 nodes. This information is crucial, because malignant spread to these distant nodes can alter patient treatment and may render a lungcancer nonresectable (17). A positive diagnosis at image-guided bronchoscopic biopsy could, therefore, limit the number of patients undergoing mediastinoscopy or the number of inappropriate surgical resections.

McAdams et al (18) recently reported on the use of virtual bronchoscopy to guide transbronchial biopsy procedures. Their results suggest that imaging guidance may improve the sensitivity for malignant nodes. The precise value of imaging guidance could not be quantified in their study, however, because only one patient in their series had previously undergone biopsy without image guidance. Although virtual imaging provides a "road map" that a bronchoscopist may view before performing TBNA, it does not provide direct guidance during the procedure. Thus, "virtual guidance" is limited by an inability to confirm correct needle placement before aspiration. This difference likely accounts for the higher sensitivity (100% vs 88% in the study of McAdams et al) of TBNA for malignant nodes in our series despite the slightly smaller mean nodal size (1.5 cm vs 1.9 cm in the study of McAdams et al).

One potential limitation of our study was the relatively small number of patients. We initially intended to perform this study in a larger cohort of patients; however, our initial success has made our pulmonary service reluctant to perform blinded biopsies without CT fluoroscopic guidance. Formulation of appropriate guidelines to determine patient selection is ongoing and will require further study.

We acknowledge that the results of our preliminary series in which a diagnosis was obtained in every case without complications may be overly optimistic. We are certain that in the future a small but currently undefined number of biopsies will be nondiagnostic despite documentation of an adequate needle position at CT fluoroscopy. Clearly, the specificity of a negative or nonmalignant diagnosis will require further validation. In addition, greater difficulty is anticipated in targeting smaller lymph nodes. Other nodes will not be able to be sampled owing to technical limitations, such as the inability to position the bronchoscope or needle into the node due to narrow tracheal anatomy or intervening cartilaginous rings. Furthermore, some lymph nodes will likely be located beyond the maximum excursion of the bronchoscopy biopsy needle. Although imaging should help minimize complications, reports of mediastinal hemorrhage or pneumothorax will undoubtedly eventually occur.

In conclusion, CT fluoroscopic guidance substantially improved the diagnostic yield of TBNA in patients who had previously undergone a nondiagnostic blinded procedure. The results of our study also confirm how difficult it is to accurately target a lesion with a conventional blinded approach. The use of CT fluoroscopic guidance during transbronchial biopsy is becoming routine at our institution, with ongoing formulation of guidelines to determine appropriate patient selection.

	FOOTNOTES

 
Abbreviation: TBNA = transbronchial needle aspiration

Author contributions: Guarantors of integrity of entire study, S.N.G., A.E.; study concepts, S.N.G., A.E., K.J.E.; study design, S.N.G., A.E.; definition of intellectual content, S.N.G., A.E.; literature research, S.N.G., A.E., P.M.B.; clinical studies, S.N.G., A.E.; data acquisition and analysis, S.N.G., A.E.; statistical analysis, S.N.G.; manuscript preparation, S.N.G., A.E., P.M.B., V.R.; manuscript editing and review, S.N.G., A.E., P.M.B., K.J.E., V.R.

	REFERENCES

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This Article Abstract Figures Only Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Goldberg, S. N. Articles by Ernst, A. Search for Related Content PubMed PubMed Citation Articles by Goldberg, S. N. Articles by Ernst, A.