Esophageal submucosal tumor diagnosed with EBUS‐guided transbronchial mediastinal cryobiopsy: A case report

Abstract Cryobiopsy is advantageous for collecting larger specimens with minimum crushing compared to forceps biopsy and transbronchial needle aspiration (TBNA), but it has not been widely used for mediastinal tumors. In this report, a leiomyoma of the thoracic esophagus was diagnosed with endobronchial ultrasound‐guided transbronchial mediastinal cryobiopsy (EBUS‐cryo). An asymptomatic 49‐year‐old woman had a 2.6‐cm sized submucosal tumor (SMT) of the esophagus adjacent to the trachea and left main bronchus. EBUS‐TBNA and EBUS‐guided intranodal forceps biopsy were performed, followed by EBUS‐cryo. The biopsy forceps could not be inserted into the tumor, but the cryoprobe was smoothly inserted. EBUS‐TBNA could not obtain enough spindle‐shaped tumor cells for immunohistochemical staining, but EBUS‐cryo provided sufficient specimens for diagnosing the leiomyoma. Adding EBUS‐cryo to EBUS‐TBNA has recently been reported to achieve high diagnostic yields for lymphomas, uncommon tumors, and benign diseases. EBUS‐cryo seems a valid diagnostic option for esophageal SMTs that are difficult to diagnose with needles and forceps.

Here, we report a case of SMT of the thoracic esophagus diagnosed with EBUS-cryo without serious complications.

CASE REPORT
A 49-year-old woman was referred for the diagnosis of a mediastinal tumor. She was asymptomatic and without a previous history of tumor. Chest computed tomography showed a 2.6-cm sized tumor adjacent to the trachea and left main bronchus, which was contiguous with the thoracic esophagus (Figure 1a For diagnosis, EBUS-TBNA, comprising three punctures with a 22-gauge needle (EchoTip Ultra; Cook Medical) and a convex probe ultrasound bronchoscope (BF-UC290F; Olympus), was performed (Figure 3a), followed by an attempt at EBUS-IFB with biopsy forceps (FB-15C1; Olympus). The forceps passed the tracheal wall through the tract formed by EBUS-TBNA but could not penetrate the tough tumor capsule (Figure 3b and Video S1), therefore we performed EBUS-cryo with a cryoprobe (20402-410; ERBE). The cryoprobe was smoothly inserted into the tumor (Figure 3c and Video S1), and two additional cryobiopsies were performed. The patient had a temporary cough without other complications ( Figure 3d).
Pathologically, EBUS-TBNA specimens showed some spindle-shaped cells, but they were insufficient for diagnostic immunostaining (Figure 4a). The cryobiopsy specimens showed proliferation of spindle-shaped tumor cells arranged in intersecting fascicles, appearing diffusely positive for desmin but negative for c-kit and DOG-1 on immunohistochemical examination (Figure 4b-d). This led to a diagnosis of leiomyoma. The tumor was observed for a year without progression.

DISCUSSION
We presented a case of esophageal SMT diagnosed with EBUS-cryo. EBUS-TBNA has high sensitivity of 88-93% for staging non-small-cell lung cancer. 3,4 However, needle-based specimens such as EBUS-TBNA and EUS-FNA are considered inadequate for immunostaining in many cases due to tissue volume, blood contamination, and crushing. 5,6,[12][13][14] The addition of EBUS-IFB or EBUS-cryo to EBUS-TBNA has been reported to have diagnostic utility, especially for lymphomas, uncommon tumors, and benign diseases. [5][6][7][8][9] A prospective study reported that only 46% of EUS-FNA specimens for SMT were immunostainable, 13 and the diagnostic yield for SMTs was insufficient, ranging from 46% to 84%, 12-14 therefore biopsy methods for SMTs with high diagnostic rates need to be established.
Cryobiopsy is widely used in transbronchoscopy and is advantageous for collecting larger specimens, with minimum crushing, compared to forceps biopsy and TBNA. [15][16][17] Although no studies have directly compared the diagnostic yields between EBUS-IFB and EBUS-cryo, EBUS-cryo may be superior to EBUS-IFB in terms of specimen quality and quantity. A randomized trial of EBUS-cryo among 197 patients reported two cases of pneumothorax (1.0%) and one case of pneumomediastinum (0.5%), without serious complications. 7 Moreover, although the safety of transesophageal cryobiopsy has not been established, a case of mediastinal tumor diagnosed as Hodgkin's lymphoma via endoscopic transesophageal cryobiopsy without complications has recently been reported. 18 To our knowledge, a transbronchial approach for esophageal SMTs has not yet been reported, but cryobiopsy, either transbronchial or transesophageal, may be a breakthrough modality for diagnosing SMTs that need to be differentiated from gastrointestinal stromal tumors and other tumors for treatment selection.
One disadvantage of EBUS-cryo and EBUS-IFB techniques is that the devices can be obstructed by the airway wall and tumor capsule during insertion into the target lesion via the tract formed by TBNA. Previous studies have reported failure rates of 10-28% in EBUS-IFB. 19,20 In the current case, forceps insertion was infeasible, but cryoprobe insertion was possible. We attribute this difference to the punctuality caused by the rigidity of devices that can apply tension against the tumor capsule. Although we used devices of approximately the same thickness, the cryoprobe was stiffer than the forceps. Despite differences in cryoprobe thickness and the method of tract creation, a randomized trial of EBUS-cryo reported all of the 196 patients could be successes except for one, who could not tolerate the TBNA procedure, 7 suggesting that the rigidity of the cryoprobe may be advantageous for its insertion into the lesion.
In conclusion, we reported a case of esophageal SMT diagnosed with EBUS-cryo. EBUS-cryo can be an option for diagnosing esophageal SMTs that are difficult to diagnose with needle-based procedures.