Substernal Thyroid Biopsy Using Endobronchial Ultrasound-guided Transbronchial Needle Aspiration

Podsumowanie

Substernal thyroid lesions are common, and need to be differentiated from malignancy. Obtaining percutaneous fine needle biopsy is not possible due to its retrosternal location. This article proposes a protocol for biopsy of substernal thyroid lesions using Endobronchial Ultrasound-guided Transbronchial Needle Aspiration (EBUS-TBNA).

Streszczenie

Substernal thyroid goiter (STG) represents about 5.8% of all mediastinal lesions¹. There is a wide variation in the published incidence rates due to the lack of a standardized definition for STG. Biopsy is often required to differentiate benign from malignant lesions. Unlike cervical thyroid, the overlying sternum precludes ultrasound-guided percutaneous fine needle aspiration of STG. Consequently, surgical mediastinoscopy is performed in the majority of cases, causing significant procedure related morbidity and cost to healthcare. Endobronchial Ultrasound-guided Transbronchial Needle Aspiration (EBUS-TBNA) is a frequently used procedure for diagnosis and staging of non-small cell lung cancer (NSCLC). Minimally invasive needle biopsy for lesions adjacent to the airways can be performed under real-time ultrasound guidance using EBUS. Its safety and efficacy is well established with over 90% sensitivity and specificity. The ability to perform EBUS as an outpatient procedure with same-day discharges offers distinct morbidity and financial advantages over surgery. As physicians performing EBUS gained procedural expertise, they have attempted to diversify its role in the diagnosis of non-lymph node thoracic pathologies. We propose here a role for EBUS-TBNA in the diagnosis of substernal thyroid lesions, along with a step-by-step protocol for the procedure.

Wprowadzenie

Substernal thyroid goiter (STG) is a slow growing tumor, eventually causing symptoms in 70-80% of cases. As per literature review, between 2.5-22.6% of STG can have malignant transformation². Compression of the trachea, esophagus, recurrent laryngeal nerve, and superior vena cava often causes symptoms like dyspnea, stridor, cough, dysphagia, dysphonia, vocal cord paralysis, Horner’s syndrome, superior vena cava syndrome, and cerebral edema. Occasional cases of overt hyperthyroidism have also been reported. A retrospective study by Shin et al. reported a positive correlation between thyroid size and presence of shortness of breath, globus sensation, and symptoms of hyperthyroidism³. This study, however, did not find a correlation between goiter size and presence of dysphagia, local discomfort, changes in voice, hemoptysis, or symptoms of hypothyroidism. Both substernal and cervical goiters carry similar malignancy risk. However, the retrosternal location makes diagnostic biopsy and treatment of STG very challenging. Most cases eventually require surgical removal using mediastinoscopy or sternotomy.

Endobronchial ultrasound (EBUS) was first described in 1992 by Hurter and Hanrath⁴. Over the years, EBUS-TBNA has become the procedure of choice for diagnosis and staging of non-small cell lung cancer. The reported sensitivity, specificity, and positive predictive value of EBUS-TBNA for mediastinal and hilar lymphadenopathy is 94%, 100%, and 100% respectively, with a low complication rate making it very safe, effective and superior to conventional TBNA⁵. However, both conventional and EBUS-guided TBNA were found to have statistically similar results for subcarinal lymph nodes⁶.

Two types of EBUS probes have been developed so far – the radial probe (RP-EBUS) and the curvilinear probe (CP-EBUS). RP-EBUS was the first one to become commercially available in 1999. It has a thin ultrasound probe inside a water-inflatable balloon tip. The probe rotates 360° at an angle perpendicular to the axis of insertion. The inflated balloon provides a circular contact for the probe, enabling it to obtain 360° view around the airways. It is used for evaluation of the central airways, assessment of airway invasion and obtaining biopsy of peripherally located lesions^7,8. After the lesion is localized, radial probe must be taken out of the guide sheath in the bronchoscope’s working channel to make way for the biopsy tool. Hence, a real-time ultrasound guided biopsy cannot be performed. Three different radial probes are currently available - 20-MHz and 30-MHz miniature probes, and the 20-MHz ultra-miniature probe. The miniature probes can be inserted through the 2.8 mm working channel of a bronchoscope and reach sub-segmental airways; the higher frequency probe provides better image resolution⁹. With an outer diameter of 1.4 mm, the ultra-miniature probe fits into the 2 mm working channel of the smaller bronchoscope and reaches more peripheral lesions.

CP-EBUS was introduced in 2005. It is a 7.5 MHz convex probe inside a saline-inflatable balloon at the tip of the bronchoscope (Figure 1). The outer diameter of the bronchoscope tube is 6.3 mm, and of the tip is 6.9 mm. The inner diameter of the working channel is 2.2 mm. The scope looks at a 35° forward oblique angle, with an angle of view of 80° (Figure 2). The convex probe itself generates a 50° image, and scans parallel to the insertion axis. Ultrasound images can be obtained by either placing the probe directly over the bronchial wall using forward flexion, or by additionally inflating the balloon with saline. Water is a better conductor than air of ultrasound waves, and improves image quality. Vascular structures can be differentiated from tissues using the color Doppler mode scan. Biopsy is performed using a dedicated 22 or 21 G TBNA needle with an echogenic-dimpled tip (Figure 3), which comes out at an angle of 20° to the long axis of the bronchoscope. The needle has a maximum extruding stroke of 40 mm, with a safety mechanism that stops it at 20 mm to prevent excessive protrusion. The internal wire of the needle minimizes sample contamination while the needle passes through the bronchial wall. It is also used to clean up the needle after it has passed through the bronchial wall and into the targeted lesion. The optimal number of aspiration “passes” is reported to be 3-7 for a satisfactory sample, but the highest yield is from the first pass^10,11. The images are processed in a dedicated ultrasound processor. Both ultrasound and white-light bronchoscopy images are simultaneously visible on the monitor, allowing for easy navigation to the site of the suspected lesion. CP-EBUS has the ability to perform real-time TBNA with direct ultrasound guidance under moderate sedation or general anesthesia. The procedure can be performed in an outpatient setting, eliminating surgery-related morbidity and need for inpatient admission.

The use of EBUS-TBNA for diagnosis of substernal thyroid is new, and has been reported in only a few case reports^12-18. Based on the review of the current literature, this paper seeks to elaborate on the procedural requirements and propose EBUS-TBNA as a modality for biopsy of substernal thyroid gland. Please note that the above equipment description is more specific to Olympus Inc. There are other commercially available products as well, and minor variations do exist.

Protokół

The protocol outlined below follows the guidelines of the institution (Roswell Park Cancer Institute, State University of New York at Buffalo, NY).

1. Initial Preparation

1. Perform Endobronchial Ultrasound-guided Transbronchial Needle Aspiration (EBUS-TBNA) under moderate sedation, monitored anesthesia care (MAC), or deep sedation and general anesthesia.
   NOTE: Patient surveys show favorable satisfaction scores with moderate sedation¹⁹, but recent data shows higher diagnostic yield using general anesthesia²⁰.
2. Optionally, perform the procedure without an airway device under moderate sedation. Use a laryngeal mask airway (LMA; size 4) for procedures involving deep sedation or general anesthesia.
   NOTE: Use LMA for lesions that are higher in the trachea. Because of the high tracheal location of substernal thyroid gland, endotracheal intubation should not be used in these cases
3. During the procedure, use the lowest effective dose of 1% or 2% lidocaine (cumulative maximum dose of ≤7 mg/kg; maximum serum level ≤5 mg/L) for topical airway anesthesia through the bronchoscope’s working channel ²¹.

2. Pre-procedure Surveillance Bronchoscopy

1. Introduce a conventional flexible bronchoscope into the airway through the oral cavity, or the LMA. Perform a sequential inspection of each sub-segment of both the left and right tracheobronchial tree for obvious endobronchial abnormalities and ensure adequate airway patency. Clean the airway of any secretion or mucus by suctioning. Remove bronchoscope from the airway when done.

3. Localizing the Lesion of Interest

1. Introduce Convex Probe-Endobronchial Ultrasound (CP-EBUS) bronchoscope with a 35° forward oblique angle view. Observe the anterior airway wall and a small portion of the adjacent lumen while advancing the bronchoscope centrally in the airway. When passing through the vocal cords, ensure that only the anterior angle of the glottic opening is visible. When in trachea, visualize the entire lumen with 35° backward flexion as needed.
2. Observe the display-screen while using the white-light bronchoscopy. Advance the bronchoscope to the estimated level of the lesion. Always, ensure that the lumen is not fully visible when advancing the bronchoscope. Full view of the lumen indicates that the tip of the CP-EBUS probe is in backward flexion, and poses the risk of traumatic scraping against the posterior airway wall.
3. After reaching the desired site of interest, inflate the balloon using about 2 ml of normal saline. Flex the tip of the CP-EBUS forward to bring it in contact with the airway.
4. Turn on the ultrasound view using the dedicated ultrasound processor. Use the two-screen display (or split-screen display) to see both the endoscopic view of the lumen, and the corresponding ultrasound image together on the screen.
5. Ensure that the EBUS bronchoscope is in flexion position. Move the CP-EBUS both clockwise and counterclockwise in small angles at the same level to identify the substernal thyroid gland. Identify the lesion. Adjust the CP-EBUS probe by moving it up-and-down so that the largest diameter of the lesion is seen.
6. Using the Doppler mode, identify the adjacent vascular structures to determine lesion’s accurate station²², and avoid accidental puncture of the blood vessels.
7. At the level of the lesion, flex the tip of the EBUS bronchoscope forward so its ultrasound probe comes in contact with the airway to obtain an ultrasound view of the lesion. When needed, flex the tip backward for full endoscopic view. Repeat the manoeuver and identify a point of entry for the TBNA needle between two tracheal rings.

4. Obtaining Endobronchial Ultrasound-guided Transbronchial Needle Biopsy

1. With the CP-EBUS tip in neutral (non-flexed) position, introduce the dedicated the 22 or 21 G TBNA needles into the working channel of the EBUS bronchoscope. Fasten the needle assembly onto the working channel using the locking mechanism.
2. Loosen the sheath adjuster knob and advance the sheath so that the tip can be barely visualized on the endoscopic image. Fasten the sheath adjuster knob now.
3. Flex the CP-EBUS probe forward to bring it in contact with the airway wall. On the ultrasound image, reconfirm that the longest diameter of the lesion is aligned with the projected path of the needle. Ensure that the needle exits the working channel at an angle of 20°.
4. Loosen the needle adjuster knob, and puncture through the airway wall into the lesion under real-time ultrasound guidance. With the EBUS needle inside the lesion, shake the internal stylet to clean out the needle tip.
5. Remove the internal stylet and attach the 20 ml vacuum-generating syringe to apply negative pressure.
6. Move the needle back-and-forth (“passes”) inside the lesion, with – 20 ml negative pressure applied by a special vacuum-generating syringe. A total of 3-7 passes is suggested based on the current literature^10,11.
7. After making sufficient number of passes, negative pressure knob is turned off, and needle is retrieved out of the working channel.
8. Push out the histological core using the internal sheath. Obtain both histological core as well as cytological aspirate by this method. Alternatively, use an air-filled 6 or 12 ml syringe to expel the content of the needle onto the slide or in the specimen cup.
9. Determine the adequateness of the specimen using on-site cytology services.

5. Post-procedure Surveillance Bronchoscopy

1. Remove the CP-EBUS bronchoscope out after biopsy. Reintroduce a conventional bronchoscope and perform a surveillance bronchoscopy to confirm absence of significant bleeding at the TBNA site. After hemostasis is ensured, remove the bronchoscope out and conclude the procedure.

Wyniki

Endobronchial Ultrasound-guided Transbronchial Needle Aspiration (EBUS-TBNA) biopsy of substernal thyroid has been reported in eight case reports as per literature review^12-18. The first case of substernal thyroid biopsy using Endobronchial Ultrasound was reported by Rosario et al. in 2006¹², wherein a CT chest done for metastatic work-up of prostate adenocarcinoma showed mediastinal lymphadenopathies. EBUS-TBNA of the lesion revealed a previously undiagnosed papillary thyroid carcinoma met...

Dyskusje

Substernal goiter was first described in 1749 by Haller²³. The reported incidence of substernal or mediastinal goiter varies between 0.2% and 45% of all goiters, depending on the definition used²⁴. More than ten definitions of substernal goiter have been proposed. By the simple clinical definition, a part of the substernal thyroid remains permanently retrosternal on physical exam without neck in hyperextension, as opposed to with neck in hyperextension as per Torre’s definition²⁵. K...

Materiały

Name	Company	Catalog Number	Comments
7.5-MHz Convex Probe-EBUS bronchoscope
Dedicated 22-gauge or 21-gauge TBNA needle
Ultrasound processor unit
On-site cytopathology (optional)
Moderate sedation drugs - Benzodiazepines or fentanyl
Deep sedation / General anesthesia drugs - Propofol or Remifentanil
Local anesthesia (for airways) - 1% or 2% Lidocaine