Clinicopathological and endoscopic ultrasonography characteristics of esophageal bronchogenic cysts: A single-center study

Abstract

BACKGROUND

Esophageal bronchogenic cysts (EBCs) are usually discovered incidentally during radiologic or endoscopic examinations. They are rare and prone to misdiagnosis or mistreatment. As a submucosal lesion, the endoscopic ultrasonography (EUS) characteristics of EBCs are unclear.

AIM

To analyze the clinicopathological and EUS characteristics of EBCs.

METHODS

A total of 22 patients with a histological diagnosis of EBCs who underwent EUS examination were retrospectively included. The clinicopathological and EUS features were collected and analyzed.

RESULTS

Most of the EBCs were asymptomatic, and no malignant transformation or precancerous changes was found histologically. Most of the EBCs were located in the lower esophagus (72.7%, 16/22). A total of 90.9% (20/22) of the EBCs originated from the muscularis propria, and 9.1% (2/22) originated from the submucosa. All of the lesions had clear boundaries. In terms of echo, 77.3% (17/22) had a hypoechoic pattern, and 22.7% (5/22) had an anechoic pattern. We found floating echoes inside the lesion, which presented as a punctiform hyperecho in 45.5% (10/22) and a flocculent hypoecho in 36.4% (8/22) of the patients. A total of 45.5% (10/22) displayed posterior wall enhancement. Fourteen patients underwent color doppler, and no blood flow signal was identified. On EUS elastography, the EBCs presented a yellow-green or green pattern (100%, 6/6). When contrast-enhanced EUS was used, the EBCs showed no enhancement (100%, 5/5).

CONCLUSION

When a submucosal lesion located at the lower esophagus originates from the intrinsic muscle layer, the possibility of EBCs should be noted, the EUS characteristics of which include a hypoecho with a clear boundary and a posterior wall enhancement, a floating echo inside and no blood flow signal, a yellow-green or green pattern on elastography, and no enhancement on contrast EUS.

Key Words: Esophageal bronchogenic cysts; Endoscopic ultrasonography; Clinicopathology; Characteristics; Diagnosis

Core Tip: Esophageal bronchogenic cysts (EBCs) are usually discovered incidentally during radiologic or endoscopic examinations. They are rare and prone to misdiagnosis or mistreatment. We retrospectively analyzed the clinicopathological and endoscopic ultrasonography features of 22 patients with EBCs. Our findings emphasize the critical role of endoscopic ultrasonography for the preoperative diagnosis and treatment of EBCs.

INTRODUCTION

Bronchogenic cysts are among the most common bronchopulmonary malformations that arise from abnormal budding of the primitive tracheobronchial tube[1,2]. The location of the cysts depends on the embryological stage of development at which abnormal budding occurs. Approximately 36%-90% of bronchogenic cysts occur in the mediastinum, and most of the remaining cysts involve the lung parenchyma[3]. Bronchogenic cysts have been reported to occur in other unusual locations, such as the pericardium[4], thymus[5], diaphragm[6], retroperitoneum[7], and cervical region[8].

Esophageal bronchogenic cysts (EBCs) are rare, and most of these lesions have been reported as individual case reports[9-12]. There are differences in reports describing their clinical features and uncertainties regarding the optimal treatment strategy[13-15]. While there may be no symptoms when lesion is relatively small, they may occur when the cyst is large, leading to narrowing of the esophagus and obstacles in food passage. Common symptoms include dysphagia, regurgitation, epigastric discomfort, and epigastric distention. Previous studies revealed that bronchogenic cysts ultimately become symptomatic over time[3,16,17]. Thus, resection of all suggested bronchogenic cysts is recommended. Nevertheless, the preoperative diagnosis of intramural EBCs is difficult. Most cases in previous reports were diagnosed as other esophageal lesions and finally confirmed by postoperative histopathology. Consequently, preoperative diagnosis is crucial.

Currently, preoperative diagnostic methods include mainly clinical imaging and endoscopy. Clinical imaging, such as computed tomography (CT) and magnetic resonance imaging (MRI), can provide information on the size, quantity, and location of the cyst in the esophageal wall. On preoperative CT, EBCs presented as well-defined, thin-wall cystic lesions with varying densities, and no enhancement of the lesions was found after the administration of contrast agent[1]. However, CT and MRI scans have difficulty detecting and displaying lesions smaller 1 cm. In previous studies, most intramural EBCs presented as subepithelial lesions under endoscopy[9,18]. Conventional endoscopic examination can provide only superficial information about protruding lesions, and endoscopic biopsy is of little significance for most cases, as the lesions present as submucosal lesions. By scanning with an ultrasound probe, endoscopic ultrasonography (EUS) can obtain information about the origin, internal echoes, blood supply, and relationship with the surrounding organs of the cysts. Nevertheless, the role of EUS in the diagnosis of EBCs has rarely been explored[19]. In the present study, we aimed to analyze the clinicopathological and EUS characteristics of EBCs.

MATERIALS AND METHODS

Inpatients with a histological diagnosis of EBCs postoperatively were screened through the pathology reports from the Zhejiang University School of Medicine First Affiliated Hospital between 2015 and 2024. Among them, patients without EUS examination or absent of EUS images were excluded. Twenty-two patients with a histological diagnosis of EBCs were included finally. The study was approved by the Ethics Committee of the Zhejiang University School of Medicine First Affiliated Hospital. Baseline demographic and clinicopathological characteristics, including clinical symptoms, sex, age at diagnosis, histopathology, and EUS and CT/MRI images, were collected. All of the included patients had complete EUS images for further analysis.

EUS

EUS was performed by experienced endoscopists at the Zhejiang University School of Medicine First Affiliated Hospital. Images were captured and stored in the system The EUS system included Olympus EU-ME2 sonogram processing equipment, an Olympus MAJ-1720 drive system, UM-DP1225R miniature ultrasonic probes with a frequency of 12 MHz, and an Olympus GF-UE260 echoendoscope (Olympus Medical System, Tokyo, Japan). Miniature ultrasonic probes were used in eight patients, and radial echoendoscopy was performed in fourteen patients. EUS were performed by endoscopic experts (over 5 years of EUS diagnosis experience). During miniature ultrasonic examination, the water immersion method was employed, allowing water to cover the lesion and serve as a medium for ultrasound. The size, location, origin, echogenic features, boundary, and blood signal were investigated. All of the EUS images were evaluated independently by 2 physicians with extensive EUS experience (over 10 years of EUS diagnosis experience). Discrepancies were resolved and came to an agreement after discussion with another physician with extensive EUS experience (over 10 years of EUS diagnosis experience).

Contrast-enhanced EUS and EUS elastography

For contrast-enhanced EUS (CE-EUS), sulfur hexafluoride microbubble (SonoVue) was used as an ultrasound contrast agent. After the SonoVue was injected into a peripheral vein, ultrasound waves disrupt it and produce a signal. An enhancement pattern of blood perfusion was observed[20]. Real-time elastography was performed using a region of interest that included at least 50% of the lesion, as well as surrounding structures. In accordance with standards reported in the international literature, red represents soft tissue, green/yellow represents intermediate organization, and blue represents hard organization[21].

Statistical analysis

Patient demographics, clinical presentations, CT results, endoscopic and EUS results, and histological information were collected and analyzed. SPSS (IBM SPSS Statistics 26; SPSS Inc., Chicago, IL, United States) was used for statistical analysis. The results are expressed as the means ± SD or the numbers (percentages).

RESULTS

Clinicopathological characteristics of the EBCs

Twenty-two patients with EBCs (mean age 47.0 ± 12.2 years) were included. The male/female ratio was 13/9. Six patients (6/22) presented symptoms, including epigastric distension (2 patients), epigastric discomfort (1 patient), and dysphagia (3 patients). Sixteen patients were asymptomatic, and their cysts were incidentally discovered via abdominal ultrasound, pulmonary CT examination or gastroscopy. The EBCs were predominantly located in the lower esophagus (72.7%, 16/22), with 27.3% (6/22) in the middle esophagus. Postoperative histological diagnoses were derived from 14 patients who underwent endoscopic treatment (2 patients with endoscopic mucosal resection, 12 patients with submucosal tunnel endoscopic resection) and 8 patients with surgery (Table 1). Visible outflow of cystic mucus during operation was identified in 14 patients. The cystic fluid was composed mainly of white (2 patients), yellow (7 patients), and brown (5 patients) cloudy mucus. A typical highly proteinaceous and mucoid yellow content was observed (Figure 1A).

Figure 1 Cystic content and histology. A: A highly proteinaceous and mucoid content during submucosal tunnel endoscopic resection; B: Histopathologic examination showing the ciliated columnar epithelium lining and smooth muscle layers in the cyst wall (hematoxylin and eosin, 5 ×); C: Histopathologic examination showing the ciliated columnar epithelium lining, smooth muscle layers and cartilage (hematoxylin and eosin, 5 ×); D: A typical pathological image showing that the lesion was originated from muscularis propria.

Table 1 Clinicopathological characteristics of the 22 esophageal bronchogenic cysts.

Characteristics	n (%)
Age	47.0 ± 12.2
Male/female	13/9
Symptoms
Epigastric distension	2 (9.1)
Epigastric discomfort	1 (4.5)
Dysphagia	3 (13.7)
Asymptomatic	16 (72.7)
Location
Lower esophagus	16 (72.7)
Middle esophagus	6 (27.3)
Treatment
Endoscopic treatment	14 (63.6)
EMR	2 (14.2)
STER	12 (85.8)
Surgery	8 (36.3)
Color of cystic fluid
White	2 (14.2)
Yellow	7 (50)
Brown	5 (35.8)
Pathology
Ciliated columnar epithelium	22 (100)
Smooth muscles	16 (72.7)
Bronchial glands	8 (36.3)
Cartilage	3 (13.7)

EMR: Endoscopic mucosal resection; STER: Submucosal tunnel endoscopic resection.

Histopathology revealed respiratory ciliated columnar epithelium-lined cyst walls with underlying smooth muscles (Figure 1B) and bronchial glands. In three patients, cartilage was identified (Figure 1C). A typical pathological image showed that the lesions was originated from muscularis propria (Figure 1D). No malignant transformation or precancerous changes were discovered via pathological analysis.

Imaging features

Eighteen patients received enhanced CT examination, three received plain CT examination, and one received enhanced MRI examination. None of the patients were preoperatively diagnosed with EBCs by CT or MRI. On CT examination, EBCs presented as suborbicular or oval low-density masses in 16 patients (Supplementary Figure 1A) and slight high-density masses in 2 patients. In one patient, plain CT revealed thickening of the esophageal wall. In two patients, lesions smaller than 1 cm were not detected on CT. The average CT value of the plain scan was 42.4 ± 16.1 HU, whereas the average enhanced CT value was 42.6 ± 13.2 HU. There was slight enhancement in two patients and no enhancement of the lesion in the other sixteen patients after the administration of contrast agent. Two patients with calcifications were identified on CT (Supplementary Figure 1B). Esophageal compression was detected in four patients (Supplementary Figure 1C).

Endoscopy and EUS characteristics

All patients had a single lesion in the esophagus. Endoscopy revealed submucosal lesions in 20 patients, which were covered by normal esophageal mucosa. The endoscopic morphology of the EBCs varied. Six patients had oblong flat bulging lesions (Figure 2A), three had nodular bulging lesions, seven had hemisphere lesions (Figure 2B), and three had dumbbell bulging lesions (Figure 2C). However, in two patients, no lesions were found in the esophageal cavity (Figure 2D).

Figure 2 White light endoscopy and endoscopic ultrasonography images of esophageal bronchogenic cysts. A: An oblong flat bulging lesion in the lower esophagus; B: A light blue hemisphere lesion in the lower esophagus; C: A dumbbell bulging lesion in the lower esophagus; D: No lesions were found in the esophageal cavity; E: A lesion originating from the muscularis propria; F: A lesion originating from the submucosa; G: A lesion with a homogeneous hypoecho; H: No blood flow signal was detected within the lesion.

The average diameter of the lesions on EUS was 3.12 ± 1.25 cm. A total of 81.8% (18/22) of the EBCs presented a predominant extraluminal growth pattern (Table 2). A total of 90.9% (20/22) of the EBCs originated from the muscularis propria (Figure 2E), and 9.1% (2/22) originated from the submucosa (Figure 2F). All of the lesions had clear boundaries. In terms of echo, 77.3% (17/22) were hypoechoic, and 22.7% (5/22) were anechoic. A total of 81.8% (18/22) of the patients had homogeneous echoes (Figure 2G), and 18.2% (4/22) had inhomogeneous echoes. Fourteen patients underwent color Doppler, and no blood flow signal was identified (100%, 14/14) (Figure 2H).

Table 2 Endoscopic ultrasonography characteristics of the 22 esophageal bronchogenic cysts.

EUS characteristics	n (%)
Average lesion size (cm)	3.12 ± 1.25
Origin
Muscularis propria	20 (90.9)
Submucosa	2 (9.1)
Growth pattern
Predominant extraluminal growth	18 (81.8)
Intraluminal growth	4 (18.2)
Margin
Smooth and clear	22 (100)
Indistinct	0 (0)
Blood flow signal	0 (0)
Echo
Hypoecho	17 (77.3)
Anecho	5 (22.7)
Punctiform hyperecho	10 (45.5)
Flocculent hypoecho	8 (36.4)
Posterior wall enhancement	10 (45.5)
EUS elastography	6
Yellow-green or green	6 (100)
Blue	0 (0)
CE-EUS
Enhancement	0 (0)
No enhancement	5 (100)

Smooth and clear the margin is clear, smooth and easy to identify through endoscopic ultrasonography. Indistinct the margin is unclear or blurry, difficult to distinguish from surrounding tissues. EUS: Endoscopic ultrasonography; CE-EUS: Contrast-enhanced endoscopic ultrasonography.

We found floating echoes (presented as a punctiform hyperecho or a flocculent hypoecho) inside the lesion. Among them, 45.5% (10/22) presented with a punctiform hyperecho inside the lesion (Figure 3A), and 36.4% (8/22) of the EBCs presented with a flocculent hypoecho (Figure 3B). A total of 45.5% (10/22) of the patients had a posterior wall enhancement (Figure 3C). In three patients, a separable zone was visible in the capsule cavity (Figure 3D). Six patients with EBCs underwent elasticity imaging, which revealed yellow–green or green patterns (100%, 6/6) (Figure 3E). Five patients with EBCs underwent CE-EUS and showed no enhancement (100%, 5/5) (Figure 3F). Invisible enhancement in the separable zone and capsule wall can be identified.

Figure 3 Special endoscopic ultrasonography findings. A: Punctiform hyperecho inside the lesion; B: Flocculent hypoecho inside the lesion; C: Posterior wall enhancement in the lesion; D: A separable zone was visible in the capsule cavity; E: Endoscopic ultrasonography elastography revealed a green pattern; F: Contrast-enhanced endoscopic ultrasonography revealed no enhancement in the capsule cavity but hypoenhancement in the separable zone and capsule wall.

DISCUSSION

EBCs are rare, and most of these lesions have been reported as individual case reports[9,15,22]. The patients with EBCs described in the literature were all diagnosed through postoperative pathology. Preoperative diagnosis is complicated because of the low incidence rate and insufficient understanding of EBCs. In the present study, we summarized the EUS characteristics of EBCs and identified several features that are useful for the preoperative diagnosis of EBCs.

We found that the lesions were located in the lower or middle esophagus, which is similar to the findings of previous studies[1,18]. Nevertheless, most of our patients were asymptomatic, even if the lesion was large. One of the reasons may be that the extracellular growth pattern of EBCs and symptoms associated with food passage obstacles are not obvious. Malignant transformation might occur due to prolonged inflammatory responses and metaplastic changes in bronchogenic cysts (BCs). Thirty-two cases of malignant transformation in BCs have been reported in the literature since 1941[1]. Therefore, in previous studies, the authors recommended active treatment for EBCs[20]. However, malignant transformation or precancerous changes of EBCs have not yet been reported according to our study and others from the literature. Whether EBCs are less likely to undergo malignant transformation than BCs in other parts of the body is unclear, and long-term follow-up is warranted.

None of the patients in our study were diagnosed with EBCs by CT or MRI preoperatively in our study. In two patients, lesions smaller than 1 cm were not detected on CT. However, these lesions were visible via endoscopy. Consequently, endoscopic examination is more sensitive than CT is for detecting EBCs. Owing to the presence of cystic fluid in EBCs, enhanced CT revealed no enhancement in most cases. Although the cystic content of bronchogenic cysts is generally at or near the water density (0-20 HU)[1], the CT value in our cohort was greater than the water density because of the highly proteinaceous and mucoid content inside the lesion. Moreover, CT cannot be used to determine whether the lesions were intramurally located within the esophagus or whether they were mediastinal outside the esophagus. In these circumstances, EUS plays an irreplaceable role in determining the origin and characteristics of the lesion.

Under EUS, 90.9% (20/22) of EBCs were found to have originated from the muscularis propria. Most of the lesions are hypoechoic and have homogeneous echoes, making it difficult to distinguish them from other hypoechoic solid lesions, such as esophageal leiomyomas. The content of protein and mucus within the cystic fluid determines the appearance of EUS to some extent. If the contents of protein and mucus secreted by the glandular epithelium of an EBC are high, the lesion under EUS is found to be hypoechoic. If the protein and mucus contents are low, it is found to be anechoic. We also detected a posterior wall enhancement in 45.5% (10/22) of the patients. Posterior wall enhancement often occurs on the posterior wall of cysts, abscesses, and other fluid areas but is almost absent from the posterior wall of vascular lumens[23]. Therefore, the presence of posterior wall enhancement indicates fluid content inside the lesion. Interestingly, a punctiform hyperecho and a flocculent low echo were also detected via EUS. We speculate that the punctiform hyperecho may originate from pigments or crystal crystals in the cystic fluid. Furthermore, owing to the uneven distribution of highly proteinaceous and mucoid content, flocculent low echoes can be observed. There is no vascular distribution inside the cyst, resulting in no blood flow signal on color Doppler. Although EUS-guided fine needle aspiration (EUS-FNA) can facilitate diagnosis through the acquisition of ciliated epithelial cells through liquid cytology, the diagnostic yield of EUS-FNA is limited in EBCs[19,24] and is subject to infection. Thus, EUS-FNA is not advocated for EBCs. By identifying these specific features, EUS helps to the diagnosis of EBCs and can distinguish EBCs from other esophageal masses, such as leiomyomas. This capability is something CT/MRI cannot replace. Therefore, EUS should be recommended as a first-line investigation for suspected EBCs.

Elastography is a real-time technique that involves the analysis of tissue stiffness[25]. Changes in tissue stiffness can be associated with various pathologies, including benign and malignant diseases. EUS-guided elastography is primarily used in the evaluation of solid pancreatic lesions[26,27] and enlarged lymph nodes[27,28] and is promising for differentiating cancer lesions from inflammatory lesions[29]. It is also used to distinguish gastrointestinal stromal tumors (GISTs) from other submucosal tumors (SMTs)[30]. Ignee et al[21] reported that 98% of gastric GISTs and 80% of gastric leiomyomas showed a blue pattern on elastography[21]. However, to our knowledge, EUS-guided elastography has not been reported for EBCs. In the present study, six EBCs presented yellow–green or green patterns on elastography. Owing to the proteinaceous and mucoid content inside the lesion, the stiffness of EBCs is usually soft, which may explain the green or yellow pattern on elastography of EBCs. This characteristic may be used to exclude other esophageal SMTs, such as esophageal leiomyomas, esophageal schwannomas, and esophageal stromal tumors.

CE-EUS was specifically developed for contrast-enhanced harmonic imaging and enables the observation of microcirculation and parenchymal perfusion in tumors. A previous systematic review revealed that CE-EUS is useful for the differential diagnosis and risk stratification of SMTs[31]. Kamata et al[32] performed CE-EUS in 58 GISTs and 15 benign SMTs. They revealed that CE-EUS discriminates GISTs from benign lesions with good accuracy. Nevertheless, CE-EUS has not been reported for EBCs. In the present study, we found no enhancement in 100% (5/5) of the EBCs. Owing to the proteinaceous or mucoid content and lack of vascular components inside the cavity, no enhancement can be detected after the injection of SonoVue. We found hypo-enhancement in the separable zone and capsule wall. These characteristics on CE-EUS may be used to differentiate esophageal lesions from solid lesions.

Definitive differentiation of EBCs from other submucosal lesions, especially esophageal leiomyomas, may be difficult. An esophageal leiomyoma is the most common submucosal lesion of the esophagus. Our previous study revealed that the location of leiomyomas in the esophagus is even in the upper, middle or lower esophagus[33]. They mainly originate from the mucosal muscularis or propria muscularis and show homogeneous hypoecho signals on EUS[34]. Although a punctiform hyperecho can be detected on EUS due to calcification inside the leiomyoma, the punctiform hyperecho is fixed and not affected by body position or ultrasound probe movement. Esophageal leiomyomas are hypoenhanced on CE-EUS[35] and blue on EUS elastography[30], which can be used to differentiate them from EBCs.

Both miniature ultrasonic probes and radial echoendoscopy were used in our study. The observation range of miniature ultrasonic probes is limited and they are not as effective as radial echoendoscopy for certain characteristics such as posterior wall enhancement or floating echo. Furthermore, radial echoendoscopy is capable of evaluating blood flow signals. Therefore, for larger lesions (> 2 cm), radial echoendoscopy is recommended. Previous studies analyzing EBCs using EUS are extremely scarce. Jiao et al[18] reported related findings. In comparison, our study included cases with larger lesion sizes and utilized a radial echoendoscope, enabling a more comprehensive and accurate analysis of internal features. Additionally, we innovatively applied EUS elastography and contrast-enhanced harmonic imaging to the diagnosis and differentiation of EBCs, which represents the first reported application of these techniques in EBCs.

EUS-based diagnosis and differentiation can guide the management of EBCs. For lesions suspected to be EBCs on EUS: If the lesion is predominantly within the muscularis propria, endoscopic resection may be recommended. If the lesion extends mostly into the mediastinum, surgical excision is the preferred approach. Additionally, given that EBCs have no reported malignant potential, cystic fluid aspiration or drainage endoscopically may be considered for EUS-suspected EBCs, avoiding unnecessary radical surgical resection. This underscores the critical role of preoperative EUS assessment in optimizing therapeutic strategies. Curative resection of EBCs by endoscopic resection poses significant challenges. In this study, 8 cases achieved an en-bloc and R0 resection, while 6 cases underwent partial resection due to the tendency for intraoperative rupture, which resulted in loss of tension and complicated complete dissection. However, partial resection combined with cauterization remains effective in preventing recurrence, which will be discussed in our next article (unpublished).

As this was a retrospective study, the lesions were dissected from the esophageal wall via endoscopic or surgical procedures rather than complete resection of the entire esophageal wall. Consequently, postoperative pathology be used to fully evaluate the origin of lesions. However, we observed that intraoperative findings could supplement postoperative pathological assessments. In the surgical group, 3 patients had lesions located in the muscular layer during the operation, with postoperative pathology showing continuity between the lesions and the muscular layer. In the submucosal tunnel endoscopic resection group, intraoperative exploration required an incision in the muscular layer within the tunnel to locate the tumors and lesions in the muscular layer were identified in 6 patients. Pathology confirmed muscular layer involvement in 3 patients. Based on combined intraoperative observations and postoperative pathological evaluations, we conclude that the lesions in part of patients originate from the muscular layer. Further prospective researches would help to determine the origin of lesions more accurately.

We acknowledge that several limitations need to be addressed in our study. First, this was a single-center retrospective study, and only a small number of patients were included. Second, EUS is associated with the risk of interobserver variation depending on observer proficiency and subjective judgment. Miniature ultrasound probes and radial echoendoscopy were used in different patients. However, images from the EBC patients were further read by a skilled EUS expert to avoid interobserver variation. Third, we did not directly compare EBCs with other submucosal lesions of the esophagus. Further studies comparing the EUS features of EBCs with those of other submucosal lesions are needed to aid in the differential diagnosis.

CONCLUSION

Most EBCs are asymptomatic, and no malignant transformation or precancerous changes are found histologically. When a submucosal lesion located at the lower esophagus originates from the intrinsic muscle layer, the possibility of EBCs should be noted. The EUS characteristics of EBCs include a hypoecho with a clear boundary and posterior wall enhancement, a floating echo inside and no blood flow signal, a yellow-green or green pattern on elastography, and no enhancement on CE-EUS. By effectively understanding the EUS characteristics of EBCs, their preoperative diagnosis becomes possible. Therefore, EUS may become a useful investigational modality for the preoperative diagnosis and treatment of EBCs.

ACKNOWLEDGEMENTS

The authors thank all the patients who provided their data at the First Affiliated Hospital of Zhejiang University who contributed to this study.