ORIGINAL INVESTIGATION
Efficacy and Safety of Transbronchial Needle Aspiration in Diagnosis and Treatment of Mediastinal Bronchogenic Cysts Systematic Review of Case Reports Venkata N. Maturu, MD, DM, Sahajal Dhooria, MD, DM, and Ritesh Agarwal, MD, DM
Background: Although surgical resection of mediastinal
bronchogenic cysts is considered the treatment of choice, there is increasing interest in minimally invasive approaches of management. The purpose of this study was to review the literature on the role of transbronchial needle aspiration (TBNA), either conventional or endobronchial ultrasound (EBUS)-guided, in the diagnosis and management of bronchogenic cysts. Methods: We systematically searched the PubMed and
EmBase databases for studies (until July 2014) reporting TBNA of bronchogenic cysts. Data were recorded on a standard data extraction form and is presented in a descriptive manner. Results: Our search yielded 26 studies (32 patients). The
median age of the patients was 43 years. Most were men (n = 15), symptomatic at presentation (n = 19), and had cysts in the paratracheal location (n = 14). Endosonography was performed on 16 patients. The EBUS appearance of the lesion was hypoechoic and anechoic in 11 and 5 patients, respectively. Thirty-one patients underwent TBNA (conventional: 16; EBUSguided: 15). The intent of TBNA was therapeutic in 19 patients and diagnostic or symptomatic palliation in the others. Complications were reported in 5 (16.1%) patients [infective (n = 4), bradycardia (n = 1)] after TBNA; there were no deaths. The median duration of follow-up was 14 months and no recurrences were detected during the follow-up period. Conclusions: Bronchoscopy is a useful tool in the diag-
nosis of bronchogenic cysts, both for confirmation of the cystic nature of the lesion by EBUS and diagnosis by TBNA (preferably EBUS-guided) of the cyst fluid. Therapeutic aspiration of the cyst may be an Received for publication September 29, 2014; accepted April 6, 2015. From the Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India. Author contributions: V.N.M.: systematically reviewed, drafted and revised the manuscript. S.D.: drafted and revised the manuscript. R.A.: conceived the idea, drafted and revised the manuscript for intellectual content. Disclosure: There is no conflict of interest or other disclosures. Reprints: Ritesh Agarwal, MD, DM, Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh-160012, India (e-mail: agarwal.ritesh@live. com). Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
J Bronchol Intervent Pulmonol
alternative to surgery in adults with mediastinal bronchogenic cysts. Key Words: bronchoscopy, endobronchial ultrasound, TBNA, EBUS, transbronchial needle aspiration (J Bronchol Intervent Pulmonol 2015;22:195–203)
C
ystic lesions of the mediastinum constitute about 12% to 18% of all mediastinal lesions in adults.1 Bronchogenic cysts are the commonest, constituting approximately 50% of all mediastinal cysts in adults.2,3 Bronchogenic cysts and esophageal duplication cysts, grouped together as foregut cysts, arise from abnormal budding of the primitive foregut. Other causes of mediastinal cysts include mesothelial cysts (pleural and pericardial cysts), neurenteric cysts, thymic cysts, cystic degeneration of malignant tumors (lymphomas, teratomas, and others), infections (tuberculosis, hydatid disease), thoracic duct cysts, and lymphangiomas. An accurate diagnosis of these cystic lesions is important for optimal management. Chest radiography, computed tomography (CT), and magnetic resonance imaging (MRI) of the chest are used in the diagnostic workup of mediastinal cysts but have their limitations. Since the last decade, endobronchial ultrasound (EBUS) is increasingly being used for the diagnosis of mediastinal lesions (lymph nodes/cysts/tumors) using both endosonographic characteristics and cytologic examination of aspirated material.4 Several treatment options are available for bronchogenic cyst including: (a) surgical resection by thoracotomy; (b) minimally invasive surgery including video-assisted thoracoscopic surgery or mediastinoscopy; (c) conservative approach with observation alone; and, (d) therapeutic aspiration of the cyst (transthoracic, transesophageal, or transbronchial). The optimal management strategy remains unclear with
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FIGURE 1. Citation selection process for the systematic review CT indicates computed tomography; EUS, endoscopic ultrasound; EUS B FNA, EUS-guided fine needle aspiration with an echobronchoscope.
surgery being the most preferred option.5–9 Herein, we systematically review the literature for the role of EBUS and transbronchial needle aspiration (TBNA) (EBUS-guided or conventional) in the management of mediastinal bronchogenic cysts in adults. METHODS
We first searched the PubMed and EmBase databases for any systematic review reporting TBNA of mediastinal bronchogenic cysts. No systematic review was found. We then
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independently searched the PubMed and EmBase databases (until July 2014) using the following free text terms: “bronchogenic cyst” AND (“endobronchial ultrasound” OR “endobronchial ultrasonography” OR “endoscopic ultrasound” OR “ebus” OR “ebus-tbna” OR “transbronchial needle aspiration” OR “transtracheal needle aspiration” OR “transcarinal needle aspiration” OR “needle aspiration” OR “aspiration”). We included case reports and case series describing TBNA of bronchogenic cysts. Editorials, reviews, abstracts, and articles not published in English
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24 24 NA 3 None None Cyst rupture None F indicates female; H, hilar; HypoE, hypoechoic; M, male; NA, not available; PT, paratracheal; Px, prophylactic; SC, subcarinal.
Not done Not done Performed Not done NA 5 5 10 9 NA ET PT SC Right H < 1/F 60/M 20/M 65/M 1 1 1 1
Respiratory failure NA Chest pain Asymptomatic
9 7 SC 31/M 1
Dyspnea
Therapeutic Therapeutic Therapeutic Therapeutic
2.5 50 50 35
No NA No Yes (Px)
36 None Not done 100
No
NA None Performed 6 SC Cough, wheeze
1
Uejima and Birmingham14 McDougall and Fromme15 Roos-Hesselink et al16 Gaugler et al17 Kramer et al18 Singh et al7 Andreani et al28
35/F
4 Kuhlman et al13
1
Respiratory failure
1 2
r
Schwartz et Barzo12
2
al11
21/F 26-77/ NA < 1/F
Facilitate anesthesia Therapeutic
60
No
NA Bradycardia Performed NA
No
NA NA None None No No Performed Not done Nil 6-70
NA Diagnosis 2.5 3 to Therapeutic 3 7 NA Relief of symptoms
Diagnosis Diagnosis Therapeutic Diagnosis 2.3 2.9 4.0 5.5 5.0 NA
Dry cough Asymptomatic Asymptomatic Chest pain, fever, dyspnea Cough Asymptomatic
Right H SC SC SC
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Schwartz et al10
61/M 48/M 26/M 27/M
SC 2-SC 2-PT PT
Not done Not done Not done Performed 3 1.5 70 80
No No No No
None None None None
NA 2 5 NA
Antibiotic Duration of FollowUse Complications up (mo) Surgical Resection Volume Aspirated (mL) Indication for Aspiration Location of Cyst Size (cm) Symptoms No. Age (y)/ Patients Sex References
TABLE 1. Details of Publications Reporting Conventional Transbronchial Needle Aspiration of Mediastinal Bronchogenic Cysts
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TBNA in Management of Mediastinal Bronchogenic Cysts
language were excluded. Any disagreement between the authors was resolved by consensus. The database created from the electronic searches was compiled in a reference manager package (Endnote X7), and all duplicate citations were eliminated. The citations were first screened by the authors to capture the relevant studies. The full text of each citation was obtained and reviewed in detail. Data were recorded on a standard data extraction sheet. The following items were extracted: (a) publication details (title, authors, and other citation details); (b) patient demographics (age, sex, and symptoms); (c) details on bronchogenic cyst (location, size of the cyst, endosonographic appearance); (d) modality used for treatment and any complications of treatment; (e) volume of fluid aspirated; (f) data on antibiotic prophylaxis; and (g) follow-up data. Data are presented in a descriptive manner. An ethics board approval was not required for this manuscript as it was a systematic review of published studies. RESULTS
Our initial database search yielded 266 references of which 26 studies (32 patients) were included for the final review (Fig. 1).7,10–34 The individual patient characteristics of the patients who underwent conventional TBNA and EBUSguided TBNA are shown in Tables 1 and 2, respectively. The pooled demographic and clinical details are shown in Table 3. The median age of the patients was 43 years (interquartile range, 26 to 61.7 y) with only 2 patients in the pediatric age group. Majority of the patients were symptomatic (n = 19), with the most common location of the cyst being paratracheal (n = 14) followed by subcarinal (n = 11). Both the children with bronchogenic cyst presented with respiratory failure due to compression of the major airways by the mediastinal cyst. Sixteen patients were managed with conventional TBNA,10–18,28 whereas 15 patients underwent EBUS-guided TBNA (14 with linear EBUS7,20–27,29–31,33 and 1 with radial EBUS19). In 1 patient, radial EBUS was only used to confirm the cystic nature of the mediastinal lesion and aspiration was not performed.32 Of the 16 patients who underwent EBUS imaging, the cyst was anechoic in 5 and hypoechoic in 11 patients. TBNA was performed with a therapeutic intent in 19 cases, whereas in others it was performed for confirmation of diagnosis (n = 10), temporary palliation of symptoms (n = 1), and facilitating anesthesia during surgery (n = 1).
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54/ Asymptomatic M 18/ Asymptomatic M 68/F Cough, stridor
37/F
2
1
1
1
1
1
1
1
Anantham et al25
Okuyama et al26
Twehues and Islam27 Aragaki-Nakahodo et al29 Gamrekeli et al30
Hong et al31
Katsenos et al32
Kuo et al33
Onuki et al34
r
56/F
NA
Cough, dyspnea Chest pain
Cough
PT
PT
LEBUS
REBUS 4.0 3.0 LEBUS 2.6 1.6 LEBUS
6.9
Left H 5.8 5.1
Right H
4.3 2.3
LEBUS PT NA LEBUS Right H NA LEBUS ET 2.4 LEBUS PT 5.6 4.0 LEBUS PT 7.0 5.7 LEBUS SC 5.4 4.2 LEBUS
PT
PT
AnE
HypoE
HypoE
HypoE
HypoE
HypoE
AnE
Therapeutic
Diagnosis
Diagnosis
Diagnosis
Therapeutic
Therapeutic
Therapeutic
Diagnostic
Diagnostic
HypoE HypoE
Therapeutic
Diagnosis
Diagnosis
Therapeutic
Therapeutic
Therapeutic
Therapeutic*
AnE
HypoE
AnE
HypoE
AnE
HypoE
HypoE
Type of EBUS Indication for EBUS Appearance Aspiration
REBUS 6.5 5.7 LEBUS 8.1 5.7 LEBUS 4.5 LEBUS 2.3 1.7 LEBUS
4.0 4.0
Size (cm)
NA
10
No
No
Yes (Px)
No
Yes (Px)
No
Not done
Performed
Not done
Not done
Performed
None
Cyst infection/ pericarditis Cyst rupture/ pneumonia None
None
None
None
None
None
None
None
Performed Yes (Px) Mediastinitis
Performed Yes (Tx)
NA
No
No
Yes (Px)
No
No
Performed Yes (Tx)
Not done
Not done
Not done
None
None
None
None
Antibiotic Use Complications
Not done Yes (Tx)
Not done
Not done
Not done
Surgical Resection
Not done Performed
NA
NA
60
150
NA
10
50
NA
5
20
20
70
NA
Volume Aspirated (mL)
NA
NA
NA
4
NA
NA
16
NA
NA
18
0.67
NA
18
1.5
12
18
Duration of Follow-up (mo)
18/ M 64/F
54/F
Chest pain
Cough, chest pain, fever Dyspnea
Asymptomatic
PT
SC
PT
PT
Location of Cyst
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*EBUS-guided aspiration done for recurrence of cyst after surgical resection. AnE indicates anechoic; F, female; H, hilar; HypoE, hypoechoic; L-EBUS, linear EBUS; M, male; NA, not available; PT, paratracheal; Px, prophylactic; R-EBUS, radial EBUS; SC, subcarinal; Tx, therapeutic.
1
1
86/ M 36/F
56/F Asymptomatic
1
Meseguer Sisternes and Franco Serrano23 Tian et al24
Fever, cough
Dyspnea
38/ M 65/ M
1
1
Dhand and Krimsky21 Casal et al22
78/ M 26/F
1
Cough, dyspnea Chest pain
Symptoms
50/F
Age (y)/ Sex
1
Galluccio and Lucantoni19 Nakajima et al20
References
No. Patients
TABLE 2. Details of Publications Reporting Endobronchial Ultrasound (EBUS)-guided Transbronchial Needle Aspiration of Mediastinal Bronchogenic Cysts
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TBNA in Management of Mediastinal Bronchogenic Cysts
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TABLE 3. Pooled Characteristics of the 32 Patients Who Underwent Conventional Transbronchial Needle Aspiration (TBNA, n = 16)/Endobronchial Ultrasonography (EBUS, n = 16)-TBNA of Mediastinal Bronchogenic Cysts Age (y) Male sex Clinical presentation Asymptomatic Cough Dyspnea Chest pain Fever Respiratory failure Location of the bronchogenic cyst Subcarinal Paratracheal Right hilar Left hilar Endotracheal Size of the cyst (cm) Endosonographic appearance Hypoechoic Anechoic Intent of TBNA Therapeutic Diagnosis Palliation of symptoms Facilitating anesthesia Volume of fluid aspirated (mL) Complications of TBNA Cyst rupture Cyst infection Bradycardia Mediastinitis Follow-up duration (mo) Antibiotics after TBNA Prophylactic Therapeutic None Surgical resection Indication of surgery* Infected cyst at presentation Complication after TBNA TBNA only done for diagnosis of cyst/palliation of symptoms
Conventional TBNA
EBUS-guided TBNA
Total
29 (20.7-60.2) 8/12 (66.67)
54 (36.2-64.7) 7/16 (43.75)
43 (26-61.7) 15/28 (53.6)
7/15 3/15 2/15 2/15 1/15 2/15
(46.67) (20) (13.34) (13.34) (6.67) (13.34)
4/15 (26.67) 6/15 (40) 4/15 (26.67) 4/15 (26.67) 2/15 (13.34) 0/15
9/16 (56.25) 4/16 (25) 2/16 (12.5) 0/16 1/16 (6.25) 5.5 (3.5-8)
2/16 (12.5) 10/16 (62.5) 2/16 (12.5) 1/16 (6.25) 1/16 (6.25) 4.9 (3.6-6.6)
— —
11/16 (68.75) 5/16 (3.12)
10/16 (62.5) 4/16 (25) 1/16 (6.25) 1/16 (6.25) 50 (3.75-70)
9/15 (60) 6/15 (40) 0/15 0/15 20 (10-65)
19/31 (61.3) 10/31 (32.3) 1/31 (3.2) 1/31 (3.2) 50 (8-70)
1/16 (6.25) 0/16 1/16 (6.25) 0/16 14.5 (2.7-27)
1/15 (66.67) 1/15 (66.67) 0/15 1/15 (66.67) 14 (2.1-18)
2/31 (6.4) 1/31 (3.2) 1/31 (3.2) 1/31 (3.2) 14 (2.7-19.5)
1/15 (6.67) 0/15 14/15 (93.33) 5/16 (31.25)
4/15 3/15 8/15 6/16
5/30 3/30 22/30 11/32
0/5 2/5 (40) 4/5 (80)
(26.67) (30) (53.33) (37.5)
3/6 (50) 2/6 (33.33) 4/6 (66.67)
11/30 9/30 6/30 6/30 3/30 2/30
(36.7) (30) (20) (20) (10) (6.7)
11/32 (34.4) 14/32 (43.7) 4/32 (12.5) 1/32 (3.12) 2/32 (6.25) 5.4 (4-6.9)
(16.7) (10) (73.3) (34.4)
3/11 (27.3) 4/11 (36.4) 8/11 (72.7)
Values are expressed as median (interquartile range) or n/N (%). *The individual values do not add up to the total as some patients had >1 indication for surgery.
In patients in whom the intent of TBNA was therapeutic, aspiration of the cyst was continued until no further fluid could be drawn (conventional TBNA) or documentation of collapse of the cyst on real-time ultrasonography (EBUS-guided TBNA). The median (range) volume of fluid aspirated per patient was 50 (8 to 70) mL [diagnostic procedure: 7.5 (2.6 to 27.5) mL, therapeutic procedure: 50 (20 to 70) mL]. Five (16.1%) patients developed complications after TBNA (Table 3); none of these were life-threatening. Four of these Copyright
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patients subsequently underwent surgical resection of the cyst. Antibiotic prophylaxis was administered in only 5 patients. One among them developed infective mediastinitis after aspiration. Of the 22 patients who did not receive prophylactic antibiotics, 3 patients developed infective complications. The follow-up details were available for 14 patients with the median duration of follow-up being 14 months. There were no instances of recurrence after therapeutic aspiration of mediastinal bronchogenic cysts.
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TABLE 4. Imaging and Cytologic Characteristics of Mediastinal Bronchogenic Cyst Method
Indications
Computed tomography
Magnetic resonance imaging Endosonography Cytology
Well-circumscribed mass adjacent to trachea/major bronchi Fluid density of the lesion (< 20 HU). Values up to 120 HU may be encountered in cysts with infection, hemorrhage, or high protein content Thin and smooth cyst wall Cyst molded to adjacent structures without significant compression effects (except in children) Well-circumscribed lesion with a low signal intensity on T1-weighted images and high signal intensity on T2-weighted images (higher T1 values in cysts with infection, hemorrhage, or high protein content) An hypoechoic (dark gray) or anechoic (black) lesion abutting the major airways Absent Doppler signal Aspiration yielding a nonbloody fluid (> 0.5 mL) Presence of only mucus or bronchial epithelial without polymorphonuclear leucocytes or lymphocytes Absence of malignant or degenerated cells Absence of hydatid scolices Negative smear for acid-fast bacilli
DISCUSSION
Bronchogenic cyst, the most common mediastinal cyst in adults, is usually located in the middle mediastinum in close proximity to the major airways and generally contains clear fluid (Table 4). The cyst wall is lined by ciliated columnar epithelium and may contain cartilage and mucus glands. In adults, bronchogenic cyst may be asymptomatic or present with nonspecific respiratory symptoms. Compression of adjacent structures causing complications is uncommon in adults. Chest radiograph is a poor modality in diagnosis of bronchogenic cysts. The cyst appears as a well-defined radiopaque mass lesion, and differentiation between solid and cystic lesion is not possible. CT chest is useful in defining the exact size of the cyst, its anatomic location within the mediastinum, and relationship to other mediastinal structures. A typical uncomplicated bronchogenic cyst usually has fluid density [Hounsfield units (HU) < 20] on CT chest. However, infected cysts and those with higher proteinaceous or calcium content may even appear solid (HU up to 120) making their differentiation from other solid lesions difficult. Up to 70% of these cysts could have soft tissue attenuation on CT chest making them indistinguishable from neoplasms.35–37 MRI has also been used in diagnosis of bronchogenic cysts. Serous fluid has a low signal intensity on T1weighted images and high signal intensity on T2weighted images. Cysts with proteinaceous fluid have a higher signal intensity on T1-weighted images. However, MRI is seldom performed in
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diagnosis of bronchogenic cysts, as it adds little to the diagnostic ability and is uncomfortable for the patient. Ultrasound provides excellent delineation between solid and cystic lesions. Cystic lesions are either hypoechoic (dark gray) or anechoic (black) on endosonography.38,39 Internal echoes within the cyst could be related to infection, hemorrhage, or the presence of proteinaceous or viscous fluid. A Doppler image can further help in identifying blood vessels. The presence of an anechoic lesion confirms the diagnosis of a mediastinal cyst; however, it is difficult to differentiate whether a hypoechoic lesion is a cyst or a necrotic mass lesion, and a needle aspiration or surgical excision is required for confirmation of the diagnosis.39 In the current review, all the 16 patients who underwent EBUS had typical appearance confirming the diagnosis of a cystic lesion with the majority of cysts being hypoechoic (68.7%). The percentage of hypoechoic bronchogenic cysts in earlier reported series of endoscopic ultrasonography varied from 15% to 70%.38–40 The most definite nonsurgical method of diagnosing a mediastinal cyst is aspiration of the fluid from the cyst. Although aspiration of the cysts can be performed percutaneously or through the esophagus or the bronchus depending on their location, TBNA (either conventional or EBUS-guided) seems to be the safest option, as most of the bronchogenic cysts lie in close apposition to the trachea and the main bronchi. The first report of TBNA in
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diagnosis of bronchogenic cyst was published in 1985 by Schwartz and colleagues. They had proposed the following criteria for diagnosing a bronchogenic cyst by TBNA: (a) aspiration yielding a significant volume of nonbloody fluid (> 0.5 mL); (b) presence of only mucus or bronchial epithelial cells as the primary cytologic component in the aspirated fluid without polymorphonuclear leucocytes or lymphocytes; (3) absence of malignant or necrotic cells; and (4) aspiration undertaken in a setting both clinically and radiographically consistent with the diagnosis of a bronchogenic cyst. In addition to the presence of ciliated epithelial cells, the presence of cartilage and detached ciliary tufts in the aspirate specimen has also been described in patients with foregut cysts.26,40 Cytology is not pathognomonic but is helpful in diagnosis of bronchogenic cyst by exclusion of other causes. It is clinically possible to make a diagnosis of bronchogenic cyst using the combination of appearance and location on CT chest and the analysis of the aspirated cyst fluid (Table 4). The presence of ciliated epithelial cells/squamous epithelial cells favors foregut duplication cysts, mesothelial cells favor pleural/pericardial cysts, lymphocyte-rich aspirate suggests thoracic duct cyst or lymphangioma, and hydatid scolices suggest a hydatid cyst. The presence of acid-fast bacilli and malignant cells clearly supports tuberculosis and cystic neoplasm, respectively. The optimal strategy for management of patients with bronchogenic cysts remains unknown.5,6 Some favor early surgical resection for all bronchogenic cysts, both symptomatic and asymptomatic.2,41 The reasons cited include: (1) possibility of developing life-threatening complications like malignancy42,43 or infection; (2) possibility of cyst enlargement causing compression of surrounding vital organs44–46; (3) higher incidence of complications when surgery is performed in symptomatic patients as opposed to asymptomatic patients41,47; and (4) ability to definitely exclude malignancy as a cause of the cystic lesion. Others favor a more conservative approach in adults when a definitive diagnosis of a benign mediastinal cyst is made nonsurgically.6,13 A conservative approach is not practical in children owing to lesser volume of the mediastinum and thus an increased tendency to cause airway compromise. Finally, most of the evidence for or against surgery comes only from case series or case reports, due to rarity of this entity. A review by Kirmani et al,48 analyzed surgical versus conservative approach (observation alone) Copyright
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for adults with asymptomatic bronchogenic cyst, and concluded that observation alone is also a feasible alternative to surgery provided a close long-term follow-up is possible. In this review, only 33 of the 74 patients (45%) who were not operated developed symptoms later. The surgical morbidity was also substantial (20%) and the difference in the postoperative complications was not significantly different between patients who were asymptomatic or symptomatic preoperatively. Importantly, in most of the reported cases of malignancy occurring in the cyst wall, the malignancy was detected at the initial presentation itself and was not a transformation during followup; further, the incidence of such coexisting malignancy was rare (0.7%).48 With the advent of endosonography and guided needle aspiration, the cysts can be safely diagnosed as being benign in nature precluding the need for surgery in most patients. Mediastinal cysts as opposed to pulmonary cysts have a lesser tendency to get infected, ruptured, or enlarged, as they rarely communicate with the airways. Hence, surgery performed for the mere purpose of excluding malignancy or the fear of future complications may not be justified in all cases.49 There is increasing interest in therapeutic aspiration for definitive management of mediastinal bronchogenic cysts, and transthoracic,50–53 transesophageal,39 and transbronchial aspiration have all been tried. The arguments against the use of this conservative strategy include: (1) infectious complications after aspiration; (2) possibility of recurrence of the cyst as the cyst wall lining remains in situ; and (3) lack of any large series of patient managed by therapeutic aspiration alone. In the current systematic review, complications occurred only in 5 patients who underwent TBNA of bronchogenic cysts. This complication rate of 16.1% is similar to the rate of complications after surgical resection.41,54 In all the 5 patients who developed complications, the complication (cyst rupture, infection, or bradycardia) was attributed directly to the aspiration and not bronchoscopy per se. Also, there is no report of recurrence of bronchogenic cyst after TBNA, although the maximum duration of follow-up available is only 3 years. Furthermore, linear EBUS provides realtime guidance and enables complete aspiration of the cyst, which is not always possible when “blind” techniques are utilized. Complete aspiration causes collapse of the cystic space, facilitating adhesion between the mucosal surfaces lining the cavity, and consequently is likely to reduce the
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recurrence rates.25 However, if a decision to perform TBNA as a definitive procedure is adopted, it is imperative to have a close follow-up of the patient to detect recurrences. The role of prophylactic antibiotics in preventing cyst infection after aspiration is currently not known. In the current review, antibiotics were administered prophylactically in 5 patients of whom 1 developed mediastinitis after the procedure. Periprocedural antibiotic prophylaxis is recommended after EBUS-guided (transesophageal) aspiration of cystic lesions.55,56 Because the flora of gastrointestinal and the respiratory tracts is not similar the need of prophylactic periprocedural antibiotics during transbronchial aspiration of bronchogenic cysts requires further investigation. There are some limitations of the current study. As it is a systematic review of case reports and series, publication bias cannot be excluded. Also, the longest follow-up duration is only 3 years. Hence, the possibility of delayed recurrence after therapeutic aspiration cannot be excluded. Further, the number of patients treated by therapeutic aspiration alone is limited. Larger case series are needed before firm conclusions can be drawn. In conclusion, bronchoscopy is a useful tool in the diagnosis of bronchogenic cysts, both for confirmation of the cystic nature of the lesion by endobronchial ultrasonography and for confirmation of the diagnosis by TBNA (conventional or EBUS-guided depending on the expertise/comfort of the operator) of the cyst fluid. Therapeutic aspiration of the cyst can be considered as an alternative to surgery in adults with bronchogenic cysts of the mediastinum, especially in those unfit or reluctant for surgery. Whether therapeutic TBNA can be used as a primary modality for management of mediastinal bronchogenic cyst in all patients is debatable. Close monitoring is required to detect any recurrence of cyst in patients managed with TBNA alone.
5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16.
17.
18. 19.
20.
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ultrasonography: a study of 165 patients. J Thorac Cardiovasc Surg. 2014;148:662–667. Fievet L, D’Journo XB, Guys JM, et al. Bronchogenic cyst: best time for surgery? Ann Thorac Surg. 2012;94: 1695–1699. Bolton JW, Shahian DM. Asymptomatic bronchogenic cysts: what is the best management? Ann Thorac Surg. 1992;53:1134–1137. Singh A, Singh S, Malpani A, et al. Treatment of bronchogenic cyst surgical versus transbronchial drainage? J Bronchology Interv Pulmonol. 2011;18:359–361. Bratu I, Laberge JM, Flageole H, et al. Foregut duplications: is there an advantage to thoracoscopic resection? J Pediatr Surg. 2005;40:138–141. Tolg C, Abelin K, Laudenbach V, et al. Open vs thorascopic surgical management of bronchogenic cysts. Surg Endosc. 2005;19:77–80. Schwartz DB, Beals TF, Wimbish KJ, et al. Transbronchial fine needle aspiration of bronchogenic cysts. Chest. 1985;88:573–575. Schwartz AR, Fishman EK, Wang KP. Diagnosis and treatment of a bronchogenic cyst using transbronchial needle aspiration. Thorax. 1986;41:326–327. Barzo P. Transbronchial mediastinal cystography. Chest. 1988;93:431–432. Kuhlman JE, Fishman EK, Wang KP, et al. Mediastinal cysts: diagnosis by CT and needle aspiration. Am J Roentgenol. 1988;150:75–78. Uejima T, Birmingham PK. Refractory bradycardia during aspiration of a tracheal cyst in a young infant. Anesthesiology. 1988;69:776–778. McDougall JC, Fromme GA. Transcarinal aspiration of a mediastinal cyst to facilitate anesthetic management. Chest. 1990;97:1490–1492. Roos-Hesselink JW, Verhoeven GT, Stoker J. Bronchogenic cyst mimicking an intracardiac mass: diagnosis by magnetic resonance imaging and treatment by needle aspiration. Heart. 1996;75:639. Gaugler C, Donato L, Rivera S, et al. Intramural bronchogenic cyst in the carina observed in a neonate and treated by needle aspiration: a case report. J Perinatol. 2004;24:317–318. Kramer MR, Shitrit D, Grubstein A. Endobronchial aspiration of bronchogenic cyst: a first report of longterm follow-up. Eur J Cardiothorac Surg. 2005;27:151. Galluccio G, Lucantoni G. Mediastinal bronchogenic cyst’s recurrence treated with EBUS-FNA with a longterm follow-up. Eur J Cardiothorac Surg. 2006;29: 627–629. discussion 629. Nakajima T, Yasufuku K, Shibuya K, et al. Endobronchial ultrasound-guided transbronchial needle aspiration for the treatment of central airway stenosis caused by a mediastinal cyst. Eur J Cardiothorac Surg. 2007;32:538–540. Dhand S, Krimsky W. Bronchogenic cyst treated by endobronchial ultrasound drainage. Thorax. 2008;63:386. Casal RF, Jimenez CA, Mehran RJ, et al. Infected mediastinal bronchogenic cyst successfully treated by endobronchial ultrasound-guided fine-needle aspiration. Ann Thorac Surg. 2010;90:e52–e53. Meseguer Sisternes M, Franco Serrano J. Drainage of a mediastinal cyst by endobronchial ultrasoundguided needle aspiration. Arch Bronconeumol. 2010;46: 207–208. r
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24. Tian Q, Chen LA, Hu H. Infectious risk enhanced because of endobronchial ultrasound-guided transbronchial needle aspiration of bronchogenic cysts. J Bronchology Interv Pulmonol. 2010;17:283–284. 25. Anantham D, Phua GC, Low SY, et al. Role of endobronchial ultrasound in the diagnosis of bronchogenic cysts. Diagn Ther Endosc. 2011;2011:468237. 26. Okuyama T, Akazawa Y, Uchida J, et al. Endotracheal bronchogenic cyst. J Bronchology Interv Pulmonol. 2011;18:340–342. 27. Twehues A, Islam S. Cystic lesions of the thorax: role of endobronchial ultrasound-guided transbronchial needle aspiration. J Bronchology Interv Pulmonol. 2011;18:265–268. 28. Andreani A, Cappiello G, Valli M, et al. TBNA for the treatment of non complicated bronchogenic cyst. Monaldi Arch Chest Dis. 2013;79:143–145. 29. Aragaki-Nakahodo AA, Guitron-Roig J, Eschenbacher W, et al. Endobronchial ultrasound-guided needle aspiration of a bronchogenic cyst to liberate from mechanical ventilation: case report and literature review. J Bronchology Interv Pulmonol. 2013;20:152–154. 30. Gamrekeli A, Kalweit G, Schafer H, et al. Infection of a bronchogenic cyst after ultrasonography-guided fine needle aspiration. Ann Thorac Surg. 2013;95: 2154–2155. 31. Hong G, Song J, Lee KJ, et al. Bronchogenic cyst rupture and pneumonia after endobronchial ultrasoundguided transbronchial needle aspiration: a case report. Tuberc Respir Dis (Seoul). 2013;74:177–180. 32. Katsenos S, Rojas-Solano J, Becker HD. Endobronchial ultrasound: a useful tool in the diagnosis of bronchogenic cyst. J Clin Imaging Sci. 2013;3:57. 33. Kuo CH, Chung FT, Kuo HP. Infected bronchogenic cyst diagnosed by endobronchial ultrasound-guided transbronchial needle aspiration. J Formos Med Assoc. 2013;112:436–437. 34. Onuki T, Kuramochi M, Inagaki M. Mediastinitis of bronchogenic cyst caused by endobronchial ultrasound-guided transbronchial needle aspiration. Respir Case Rep. 2013;2:73–75. 35. McAdams HP, Kirejczyk WM, Rosado-de-Christenson ML, et al. Bronchogenic cyst: imaging features with clinical and histopathologic correlation. Radiology. 2000;217:441–446. 36. Kanemitsu Y, Nakayama H, Asamura H, et al. Clinical features and management of bronchogenic cysts: report of 17 cases. Surg Today. 1999;29:1201–1205. 37. Vos CG, Hartemink KJ, Golding RP, et al. Bronchogenic cysts in adults: frequently mistaken for a solid mass on computed tomography. Wien Klin Wochenschr. 2011;123:179–182. 38. Wildi SM, Hoda RS, Fickling W, et al. Diagnosis of benign cysts of the mediastinum: the role and risks of EUS and FNA. Gastrointest Endosc. 2003;58:362–368. 39. Fazel A, Moezardalan K, Varadarajulu S, et al. The utility and the safety of EUS-guided FNA in the evaluation of duplication cysts. Gastrointest Endosc. 2005;62:575–580.
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40. Eloubeidi MA, Cohn M, Cerfolio RJ, et al. Endoscopic ultrasound-guided fine-needle aspiration in the diagnosis of foregut duplication cysts: the value of demonstrating detached ciliary tufts in cyst fluid. Cancer. 2004;102:253–258. 41. Patel SR, Meeker DP, Biscotti CV, et al. Presentation and management of bronchogenic cysts in the adult. Chest. 1994;106:79–85. 42. Fiorelli A, Rambaldi P, Accardo M, et al. Malignant transformation of bronchogenic cyst revealed by 99mTc-MIBI-SPECT. Asian Cardiovasc Thorac Ann. 2012;20:347–349. 43. Kurpat D, Rothe G, Haupt R. Carcinoma in the wall of a congenital bronchial cyst. Z Erkr Atmungsorgane. 1974;139:109–115. 44. Kennebeck GA, Wong AK, Berry WR, et al. Mediastinal bronchogenic cyst manifesting as a catastrophic myocardial infarction. Ann Thorac Surg. 1999;67:1789–1791. 45. Worsnop CJ, Teichtahl H, Clarke CP. Bronchogenic cyst: a cause of pulmonary artery obstruction and breathlessness. Ann Thorac Surg. 1993;55:1254–1255. 46. Rammohan G, Berger HW, Lajam F, et al. Superior vena cava syndrome caused by bronchogenic cyst. Chest. 1975;68:599–601. 47. Granato F, Voltolini L, Ghiribelli C, et al. Surgery for bronchogenic cysts: always easy? Asian Cardiovasc Thorac Ann. 2009;17:467–471. 48. Kirmani B, Kirmani B, Sogliani F. Should asymptomatic bronchogenic cysts in adults be treated conservatively or with surgery? Interact Cardiovasc Thorac Surg. 2010;11:649–659. 49. Ponn RB. Simple mediastinal cysts: resect them all? Chest. 2003;124:4–6. 50. Li L, Zeng XQ, Li YH. CT-guided percutaneous largeneedle aspiration and bleomycin sclerotherapy for bronchogenic cyst: report of four cases. J Vasc Interv Radiol. 2010;21:1045–1049. 51. Le Guen Y, Hureaux J, Gagnadoux F, et al. Treatment of a compressive bronchogenic cyst by computed tomography-guided needle aspiration. Rev Mal Respir. 2005;22:481–484. 52. Whyte MK, Dollery CT, Adam A, et al. Central bronchogenic cyst: treatment by extrapleural percutaneous aspiration. Bmj. 1989;299:1457–1458. 53. Pesek M, Chudacek Z. Diagnosis and treatment of mediastinal cyst using transparietal needle aspiration. Z Erkr Atmungsorgane. 1987;169:157–161. 54. Limaiem F, Ayadi-Kaddour A, Djilani H, et al. Pulmonary and mediastinal bronchogenic cysts: a clinicopathologic study of 33 cases. Lung. 2008;186: 55–61. 55. Annema JT, Veselic M, Versteegh MI, et al. Mediastinitis caused by EUS-FNA of a bronchogenic cyst. Endoscopy. 2003;35:791–793. 56. Committee ASoP, Early DS, Acosta RD, et al. Adverse events associated with EUS and EUS with FNA. Gastrointest Endosc. 2013;77:839–843.
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203
Efficacy and Safety of Transbronchial Needle Aspiration in Diagnosis and Treatment of Mediastinal Bronchogenic Cysts Systematic Review of Case Reports Venkata N. Maturu, MD, DM, Sahajal Dhooria, MD, DM, and Ritesh Agarwal, MD, DM
Background: Although surgical resection of mediastinal
bronchogenic cysts is considered the treatment of choice, there is increasing interest in minimally invasive approaches of management. The purpose of this study was to review the literature on the role of transbronchial needle aspiration (TBNA), either conventional or endobronchial ultrasound (EBUS)-guided, in the diagnosis and management of bronchogenic cysts. Methods: We systematically searched the PubMed and
EmBase databases for studies (until July 2014) reporting TBNA of bronchogenic cysts. Data were recorded on a standard data extraction form and is presented in a descriptive manner. Results: Our search yielded 26 studies (32 patients). The
median age of the patients was 43 years. Most were men (n = 15), symptomatic at presentation (n = 19), and had cysts in the paratracheal location (n = 14). Endosonography was performed on 16 patients. The EBUS appearance of the lesion was hypoechoic and anechoic in 11 and 5 patients, respectively. Thirty-one patients underwent TBNA (conventional: 16; EBUSguided: 15). The intent of TBNA was therapeutic in 19 patients and diagnostic or symptomatic palliation in the others. Complications were reported in 5 (16.1%) patients [infective (n = 4), bradycardia (n = 1)] after TBNA; there were no deaths. The median duration of follow-up was 14 months and no recurrences were detected during the follow-up period. Conclusions: Bronchoscopy is a useful tool in the diag-
nosis of bronchogenic cysts, both for confirmation of the cystic nature of the lesion by EBUS and diagnosis by TBNA (preferably EBUS-guided) of the cyst fluid. Therapeutic aspiration of the cyst may be an Received for publication September 29, 2014; accepted April 6, 2015. From the Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India. Author contributions: V.N.M.: systematically reviewed, drafted and revised the manuscript. S.D.: drafted and revised the manuscript. R.A.: conceived the idea, drafted and revised the manuscript for intellectual content. Disclosure: There is no conflict of interest or other disclosures. Reprints: Ritesh Agarwal, MD, DM, Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh-160012, India (e-mail: agarwal.ritesh@live. com). Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
J Bronchol Intervent Pulmonol
alternative to surgery in adults with mediastinal bronchogenic cysts. Key Words: bronchoscopy, endobronchial ultrasound, TBNA, EBUS, transbronchial needle aspiration (J Bronchol Intervent Pulmonol 2015;22:195–203)
C
ystic lesions of the mediastinum constitute about 12% to 18% of all mediastinal lesions in adults.1 Bronchogenic cysts are the commonest, constituting approximately 50% of all mediastinal cysts in adults.2,3 Bronchogenic cysts and esophageal duplication cysts, grouped together as foregut cysts, arise from abnormal budding of the primitive foregut. Other causes of mediastinal cysts include mesothelial cysts (pleural and pericardial cysts), neurenteric cysts, thymic cysts, cystic degeneration of malignant tumors (lymphomas, teratomas, and others), infections (tuberculosis, hydatid disease), thoracic duct cysts, and lymphangiomas. An accurate diagnosis of these cystic lesions is important for optimal management. Chest radiography, computed tomography (CT), and magnetic resonance imaging (MRI) of the chest are used in the diagnostic workup of mediastinal cysts but have their limitations. Since the last decade, endobronchial ultrasound (EBUS) is increasingly being used for the diagnosis of mediastinal lesions (lymph nodes/cysts/tumors) using both endosonographic characteristics and cytologic examination of aspirated material.4 Several treatment options are available for bronchogenic cyst including: (a) surgical resection by thoracotomy; (b) minimally invasive surgery including video-assisted thoracoscopic surgery or mediastinoscopy; (c) conservative approach with observation alone; and, (d) therapeutic aspiration of the cyst (transthoracic, transesophageal, or transbronchial). The optimal management strategy remains unclear with
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FIGURE 1. Citation selection process for the systematic review CT indicates computed tomography; EUS, endoscopic ultrasound; EUS B FNA, EUS-guided fine needle aspiration with an echobronchoscope.
surgery being the most preferred option.5–9 Herein, we systematically review the literature for the role of EBUS and transbronchial needle aspiration (TBNA) (EBUS-guided or conventional) in the management of mediastinal bronchogenic cysts in adults. METHODS
We first searched the PubMed and EmBase databases for any systematic review reporting TBNA of mediastinal bronchogenic cysts. No systematic review was found. We then
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independently searched the PubMed and EmBase databases (until July 2014) using the following free text terms: “bronchogenic cyst” AND (“endobronchial ultrasound” OR “endobronchial ultrasonography” OR “endoscopic ultrasound” OR “ebus” OR “ebus-tbna” OR “transbronchial needle aspiration” OR “transtracheal needle aspiration” OR “transcarinal needle aspiration” OR “needle aspiration” OR “aspiration”). We included case reports and case series describing TBNA of bronchogenic cysts. Editorials, reviews, abstracts, and articles not published in English
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24 24 NA 3 None None Cyst rupture None F indicates female; H, hilar; HypoE, hypoechoic; M, male; NA, not available; PT, paratracheal; Px, prophylactic; SC, subcarinal.
Not done Not done Performed Not done NA 5 5 10 9 NA ET PT SC Right H < 1/F 60/M 20/M 65/M 1 1 1 1
Respiratory failure NA Chest pain Asymptomatic
9 7 SC 31/M 1
Dyspnea
Therapeutic Therapeutic Therapeutic Therapeutic
2.5 50 50 35
No NA No Yes (Px)
36 None Not done 100
No
NA None Performed 6 SC Cough, wheeze
1
Uejima and Birmingham14 McDougall and Fromme15 Roos-Hesselink et al16 Gaugler et al17 Kramer et al18 Singh et al7 Andreani et al28
35/F
4 Kuhlman et al13
1
Respiratory failure
1 2
r
Schwartz et Barzo12
2
al11
21/F 26-77/ NA < 1/F
Facilitate anesthesia Therapeutic
60
No
NA Bradycardia Performed NA
No
NA NA None None No No Performed Not done Nil 6-70
NA Diagnosis 2.5 3 to Therapeutic 3 7 NA Relief of symptoms
Diagnosis Diagnosis Therapeutic Diagnosis 2.3 2.9 4.0 5.5 5.0 NA
Dry cough Asymptomatic Asymptomatic Chest pain, fever, dyspnea Cough Asymptomatic
Right H SC SC SC
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Schwartz et al10
61/M 48/M 26/M 27/M
SC 2-SC 2-PT PT
Not done Not done Not done Performed 3 1.5 70 80
No No No No
None None None None
NA 2 5 NA
Antibiotic Duration of FollowUse Complications up (mo) Surgical Resection Volume Aspirated (mL) Indication for Aspiration Location of Cyst Size (cm) Symptoms No. Age (y)/ Patients Sex References
TABLE 1. Details of Publications Reporting Conventional Transbronchial Needle Aspiration of Mediastinal Bronchogenic Cysts
J Bronchol Intervent Pulmonol
TBNA in Management of Mediastinal Bronchogenic Cysts
language were excluded. Any disagreement between the authors was resolved by consensus. The database created from the electronic searches was compiled in a reference manager package (Endnote X7), and all duplicate citations were eliminated. The citations were first screened by the authors to capture the relevant studies. The full text of each citation was obtained and reviewed in detail. Data were recorded on a standard data extraction sheet. The following items were extracted: (a) publication details (title, authors, and other citation details); (b) patient demographics (age, sex, and symptoms); (c) details on bronchogenic cyst (location, size of the cyst, endosonographic appearance); (d) modality used for treatment and any complications of treatment; (e) volume of fluid aspirated; (f) data on antibiotic prophylaxis; and (g) follow-up data. Data are presented in a descriptive manner. An ethics board approval was not required for this manuscript as it was a systematic review of published studies. RESULTS
Our initial database search yielded 266 references of which 26 studies (32 patients) were included for the final review (Fig. 1).7,10–34 The individual patient characteristics of the patients who underwent conventional TBNA and EBUSguided TBNA are shown in Tables 1 and 2, respectively. The pooled demographic and clinical details are shown in Table 3. The median age of the patients was 43 years (interquartile range, 26 to 61.7 y) with only 2 patients in the pediatric age group. Majority of the patients were symptomatic (n = 19), with the most common location of the cyst being paratracheal (n = 14) followed by subcarinal (n = 11). Both the children with bronchogenic cyst presented with respiratory failure due to compression of the major airways by the mediastinal cyst. Sixteen patients were managed with conventional TBNA,10–18,28 whereas 15 patients underwent EBUS-guided TBNA (14 with linear EBUS7,20–27,29–31,33 and 1 with radial EBUS19). In 1 patient, radial EBUS was only used to confirm the cystic nature of the mediastinal lesion and aspiration was not performed.32 Of the 16 patients who underwent EBUS imaging, the cyst was anechoic in 5 and hypoechoic in 11 patients. TBNA was performed with a therapeutic intent in 19 cases, whereas in others it was performed for confirmation of diagnosis (n = 10), temporary palliation of symptoms (n = 1), and facilitating anesthesia during surgery (n = 1).
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54/ Asymptomatic M 18/ Asymptomatic M 68/F Cough, stridor
37/F
2
1
1
1
1
1
1
1
Anantham et al25
Okuyama et al26
Twehues and Islam27 Aragaki-Nakahodo et al29 Gamrekeli et al30
Hong et al31
Katsenos et al32
Kuo et al33
Onuki et al34
r
56/F
NA
Cough, dyspnea Chest pain
Cough
PT
PT
LEBUS
REBUS 4.0 3.0 LEBUS 2.6 1.6 LEBUS
6.9
Left H 5.8 5.1
Right H
4.3 2.3
LEBUS PT NA LEBUS Right H NA LEBUS ET 2.4 LEBUS PT 5.6 4.0 LEBUS PT 7.0 5.7 LEBUS SC 5.4 4.2 LEBUS
PT
PT
AnE
HypoE
HypoE
HypoE
HypoE
HypoE
AnE
Therapeutic
Diagnosis
Diagnosis
Diagnosis
Therapeutic
Therapeutic
Therapeutic
Diagnostic
Diagnostic
HypoE HypoE
Therapeutic
Diagnosis
Diagnosis
Therapeutic
Therapeutic
Therapeutic
Therapeutic*
AnE
HypoE
AnE
HypoE
AnE
HypoE
HypoE
Type of EBUS Indication for EBUS Appearance Aspiration
REBUS 6.5 5.7 LEBUS 8.1 5.7 LEBUS 4.5 LEBUS 2.3 1.7 LEBUS
4.0 4.0
Size (cm)
NA
10
No
No
Yes (Px)
No
Yes (Px)
No
Not done
Performed
Not done
Not done
Performed
None
Cyst infection/ pericarditis Cyst rupture/ pneumonia None
None
None
None
None
None
None
None
Performed Yes (Px) Mediastinitis
Performed Yes (Tx)
NA
No
No
Yes (Px)
No
No
Performed Yes (Tx)
Not done
Not done
Not done
None
None
None
None
Antibiotic Use Complications
Not done Yes (Tx)
Not done
Not done
Not done
Surgical Resection
Not done Performed
NA
NA
60
150
NA
10
50
NA
5
20
20
70
NA
Volume Aspirated (mL)
NA
NA
NA
4
NA
NA
16
NA
NA
18
0.67
NA
18
1.5
12
18
Duration of Follow-up (mo)
18/ M 64/F
54/F
Chest pain
Cough, chest pain, fever Dyspnea
Asymptomatic
PT
SC
PT
PT
Location of Cyst
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*EBUS-guided aspiration done for recurrence of cyst after surgical resection. AnE indicates anechoic; F, female; H, hilar; HypoE, hypoechoic; L-EBUS, linear EBUS; M, male; NA, not available; PT, paratracheal; Px, prophylactic; R-EBUS, radial EBUS; SC, subcarinal; Tx, therapeutic.
1
1
86/ M 36/F
56/F Asymptomatic
1
Meseguer Sisternes and Franco Serrano23 Tian et al24
Fever, cough
Dyspnea
38/ M 65/ M
1
1
Dhand and Krimsky21 Casal et al22
78/ M 26/F
1
Cough, dyspnea Chest pain
Symptoms
50/F
Age (y)/ Sex
1
Galluccio and Lucantoni19 Nakajima et al20
References
No. Patients
TABLE 2. Details of Publications Reporting Endobronchial Ultrasound (EBUS)-guided Transbronchial Needle Aspiration of Mediastinal Bronchogenic Cysts
Maturu et al Volume 22, Number 3, July 2015
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TBNA in Management of Mediastinal Bronchogenic Cysts
Volume 22, Number 3, July 2015
TABLE 3. Pooled Characteristics of the 32 Patients Who Underwent Conventional Transbronchial Needle Aspiration (TBNA, n = 16)/Endobronchial Ultrasonography (EBUS, n = 16)-TBNA of Mediastinal Bronchogenic Cysts Age (y) Male sex Clinical presentation Asymptomatic Cough Dyspnea Chest pain Fever Respiratory failure Location of the bronchogenic cyst Subcarinal Paratracheal Right hilar Left hilar Endotracheal Size of the cyst (cm) Endosonographic appearance Hypoechoic Anechoic Intent of TBNA Therapeutic Diagnosis Palliation of symptoms Facilitating anesthesia Volume of fluid aspirated (mL) Complications of TBNA Cyst rupture Cyst infection Bradycardia Mediastinitis Follow-up duration (mo) Antibiotics after TBNA Prophylactic Therapeutic None Surgical resection Indication of surgery* Infected cyst at presentation Complication after TBNA TBNA only done for diagnosis of cyst/palliation of symptoms
Conventional TBNA
EBUS-guided TBNA
Total
29 (20.7-60.2) 8/12 (66.67)
54 (36.2-64.7) 7/16 (43.75)
43 (26-61.7) 15/28 (53.6)
7/15 3/15 2/15 2/15 1/15 2/15
(46.67) (20) (13.34) (13.34) (6.67) (13.34)
4/15 (26.67) 6/15 (40) 4/15 (26.67) 4/15 (26.67) 2/15 (13.34) 0/15
9/16 (56.25) 4/16 (25) 2/16 (12.5) 0/16 1/16 (6.25) 5.5 (3.5-8)
2/16 (12.5) 10/16 (62.5) 2/16 (12.5) 1/16 (6.25) 1/16 (6.25) 4.9 (3.6-6.6)
— —
11/16 (68.75) 5/16 (3.12)
10/16 (62.5) 4/16 (25) 1/16 (6.25) 1/16 (6.25) 50 (3.75-70)
9/15 (60) 6/15 (40) 0/15 0/15 20 (10-65)
19/31 (61.3) 10/31 (32.3) 1/31 (3.2) 1/31 (3.2) 50 (8-70)
1/16 (6.25) 0/16 1/16 (6.25) 0/16 14.5 (2.7-27)
1/15 (66.67) 1/15 (66.67) 0/15 1/15 (66.67) 14 (2.1-18)
2/31 (6.4) 1/31 (3.2) 1/31 (3.2) 1/31 (3.2) 14 (2.7-19.5)
1/15 (6.67) 0/15 14/15 (93.33) 5/16 (31.25)
4/15 3/15 8/15 6/16
5/30 3/30 22/30 11/32
0/5 2/5 (40) 4/5 (80)
(26.67) (30) (53.33) (37.5)
3/6 (50) 2/6 (33.33) 4/6 (66.67)
11/30 9/30 6/30 6/30 3/30 2/30
(36.7) (30) (20) (20) (10) (6.7)
11/32 (34.4) 14/32 (43.7) 4/32 (12.5) 1/32 (3.12) 2/32 (6.25) 5.4 (4-6.9)
(16.7) (10) (73.3) (34.4)
3/11 (27.3) 4/11 (36.4) 8/11 (72.7)
Values are expressed as median (interquartile range) or n/N (%). *The individual values do not add up to the total as some patients had >1 indication for surgery.
In patients in whom the intent of TBNA was therapeutic, aspiration of the cyst was continued until no further fluid could be drawn (conventional TBNA) or documentation of collapse of the cyst on real-time ultrasonography (EBUS-guided TBNA). The median (range) volume of fluid aspirated per patient was 50 (8 to 70) mL [diagnostic procedure: 7.5 (2.6 to 27.5) mL, therapeutic procedure: 50 (20 to 70) mL]. Five (16.1%) patients developed complications after TBNA (Table 3); none of these were life-threatening. Four of these Copyright
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patients subsequently underwent surgical resection of the cyst. Antibiotic prophylaxis was administered in only 5 patients. One among them developed infective mediastinitis after aspiration. Of the 22 patients who did not receive prophylactic antibiotics, 3 patients developed infective complications. The follow-up details were available for 14 patients with the median duration of follow-up being 14 months. There were no instances of recurrence after therapeutic aspiration of mediastinal bronchogenic cysts.
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TABLE 4. Imaging and Cytologic Characteristics of Mediastinal Bronchogenic Cyst Method
Indications
Computed tomography
Magnetic resonance imaging Endosonography Cytology
Well-circumscribed mass adjacent to trachea/major bronchi Fluid density of the lesion (< 20 HU). Values up to 120 HU may be encountered in cysts with infection, hemorrhage, or high protein content Thin and smooth cyst wall Cyst molded to adjacent structures without significant compression effects (except in children) Well-circumscribed lesion with a low signal intensity on T1-weighted images and high signal intensity on T2-weighted images (higher T1 values in cysts with infection, hemorrhage, or high protein content) An hypoechoic (dark gray) or anechoic (black) lesion abutting the major airways Absent Doppler signal Aspiration yielding a nonbloody fluid (> 0.5 mL) Presence of only mucus or bronchial epithelial without polymorphonuclear leucocytes or lymphocytes Absence of malignant or degenerated cells Absence of hydatid scolices Negative smear for acid-fast bacilli
DISCUSSION
Bronchogenic cyst, the most common mediastinal cyst in adults, is usually located in the middle mediastinum in close proximity to the major airways and generally contains clear fluid (Table 4). The cyst wall is lined by ciliated columnar epithelium and may contain cartilage and mucus glands. In adults, bronchogenic cyst may be asymptomatic or present with nonspecific respiratory symptoms. Compression of adjacent structures causing complications is uncommon in adults. Chest radiograph is a poor modality in diagnosis of bronchogenic cysts. The cyst appears as a well-defined radiopaque mass lesion, and differentiation between solid and cystic lesion is not possible. CT chest is useful in defining the exact size of the cyst, its anatomic location within the mediastinum, and relationship to other mediastinal structures. A typical uncomplicated bronchogenic cyst usually has fluid density [Hounsfield units (HU) < 20] on CT chest. However, infected cysts and those with higher proteinaceous or calcium content may even appear solid (HU up to 120) making their differentiation from other solid lesions difficult. Up to 70% of these cysts could have soft tissue attenuation on CT chest making them indistinguishable from neoplasms.35–37 MRI has also been used in diagnosis of bronchogenic cysts. Serous fluid has a low signal intensity on T1weighted images and high signal intensity on T2weighted images. Cysts with proteinaceous fluid have a higher signal intensity on T1-weighted images. However, MRI is seldom performed in
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diagnosis of bronchogenic cysts, as it adds little to the diagnostic ability and is uncomfortable for the patient. Ultrasound provides excellent delineation between solid and cystic lesions. Cystic lesions are either hypoechoic (dark gray) or anechoic (black) on endosonography.38,39 Internal echoes within the cyst could be related to infection, hemorrhage, or the presence of proteinaceous or viscous fluid. A Doppler image can further help in identifying blood vessels. The presence of an anechoic lesion confirms the diagnosis of a mediastinal cyst; however, it is difficult to differentiate whether a hypoechoic lesion is a cyst or a necrotic mass lesion, and a needle aspiration or surgical excision is required for confirmation of the diagnosis.39 In the current review, all the 16 patients who underwent EBUS had typical appearance confirming the diagnosis of a cystic lesion with the majority of cysts being hypoechoic (68.7%). The percentage of hypoechoic bronchogenic cysts in earlier reported series of endoscopic ultrasonography varied from 15% to 70%.38–40 The most definite nonsurgical method of diagnosing a mediastinal cyst is aspiration of the fluid from the cyst. Although aspiration of the cysts can be performed percutaneously or through the esophagus or the bronchus depending on their location, TBNA (either conventional or EBUS-guided) seems to be the safest option, as most of the bronchogenic cysts lie in close apposition to the trachea and the main bronchi. The first report of TBNA in
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diagnosis of bronchogenic cyst was published in 1985 by Schwartz and colleagues. They had proposed the following criteria for diagnosing a bronchogenic cyst by TBNA: (a) aspiration yielding a significant volume of nonbloody fluid (> 0.5 mL); (b) presence of only mucus or bronchial epithelial cells as the primary cytologic component in the aspirated fluid without polymorphonuclear leucocytes or lymphocytes; (3) absence of malignant or necrotic cells; and (4) aspiration undertaken in a setting both clinically and radiographically consistent with the diagnosis of a bronchogenic cyst. In addition to the presence of ciliated epithelial cells, the presence of cartilage and detached ciliary tufts in the aspirate specimen has also been described in patients with foregut cysts.26,40 Cytology is not pathognomonic but is helpful in diagnosis of bronchogenic cyst by exclusion of other causes. It is clinically possible to make a diagnosis of bronchogenic cyst using the combination of appearance and location on CT chest and the analysis of the aspirated cyst fluid (Table 4). The presence of ciliated epithelial cells/squamous epithelial cells favors foregut duplication cysts, mesothelial cells favor pleural/pericardial cysts, lymphocyte-rich aspirate suggests thoracic duct cyst or lymphangioma, and hydatid scolices suggest a hydatid cyst. The presence of acid-fast bacilli and malignant cells clearly supports tuberculosis and cystic neoplasm, respectively. The optimal strategy for management of patients with bronchogenic cysts remains unknown.5,6 Some favor early surgical resection for all bronchogenic cysts, both symptomatic and asymptomatic.2,41 The reasons cited include: (1) possibility of developing life-threatening complications like malignancy42,43 or infection; (2) possibility of cyst enlargement causing compression of surrounding vital organs44–46; (3) higher incidence of complications when surgery is performed in symptomatic patients as opposed to asymptomatic patients41,47; and (4) ability to definitely exclude malignancy as a cause of the cystic lesion. Others favor a more conservative approach in adults when a definitive diagnosis of a benign mediastinal cyst is made nonsurgically.6,13 A conservative approach is not practical in children owing to lesser volume of the mediastinum and thus an increased tendency to cause airway compromise. Finally, most of the evidence for or against surgery comes only from case series or case reports, due to rarity of this entity. A review by Kirmani et al,48 analyzed surgical versus conservative approach (observation alone) Copyright
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for adults with asymptomatic bronchogenic cyst, and concluded that observation alone is also a feasible alternative to surgery provided a close long-term follow-up is possible. In this review, only 33 of the 74 patients (45%) who were not operated developed symptoms later. The surgical morbidity was also substantial (20%) and the difference in the postoperative complications was not significantly different between patients who were asymptomatic or symptomatic preoperatively. Importantly, in most of the reported cases of malignancy occurring in the cyst wall, the malignancy was detected at the initial presentation itself and was not a transformation during followup; further, the incidence of such coexisting malignancy was rare (0.7%).48 With the advent of endosonography and guided needle aspiration, the cysts can be safely diagnosed as being benign in nature precluding the need for surgery in most patients. Mediastinal cysts as opposed to pulmonary cysts have a lesser tendency to get infected, ruptured, or enlarged, as they rarely communicate with the airways. Hence, surgery performed for the mere purpose of excluding malignancy or the fear of future complications may not be justified in all cases.49 There is increasing interest in therapeutic aspiration for definitive management of mediastinal bronchogenic cysts, and transthoracic,50–53 transesophageal,39 and transbronchial aspiration have all been tried. The arguments against the use of this conservative strategy include: (1) infectious complications after aspiration; (2) possibility of recurrence of the cyst as the cyst wall lining remains in situ; and (3) lack of any large series of patient managed by therapeutic aspiration alone. In the current systematic review, complications occurred only in 5 patients who underwent TBNA of bronchogenic cysts. This complication rate of 16.1% is similar to the rate of complications after surgical resection.41,54 In all the 5 patients who developed complications, the complication (cyst rupture, infection, or bradycardia) was attributed directly to the aspiration and not bronchoscopy per se. Also, there is no report of recurrence of bronchogenic cyst after TBNA, although the maximum duration of follow-up available is only 3 years. Furthermore, linear EBUS provides realtime guidance and enables complete aspiration of the cyst, which is not always possible when “blind” techniques are utilized. Complete aspiration causes collapse of the cystic space, facilitating adhesion between the mucosal surfaces lining the cavity, and consequently is likely to reduce the
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recurrence rates.25 However, if a decision to perform TBNA as a definitive procedure is adopted, it is imperative to have a close follow-up of the patient to detect recurrences. The role of prophylactic antibiotics in preventing cyst infection after aspiration is currently not known. In the current review, antibiotics were administered prophylactically in 5 patients of whom 1 developed mediastinitis after the procedure. Periprocedural antibiotic prophylaxis is recommended after EBUS-guided (transesophageal) aspiration of cystic lesions.55,56 Because the flora of gastrointestinal and the respiratory tracts is not similar the need of prophylactic periprocedural antibiotics during transbronchial aspiration of bronchogenic cysts requires further investigation. There are some limitations of the current study. As it is a systematic review of case reports and series, publication bias cannot be excluded. Also, the longest follow-up duration is only 3 years. Hence, the possibility of delayed recurrence after therapeutic aspiration cannot be excluded. Further, the number of patients treated by therapeutic aspiration alone is limited. Larger case series are needed before firm conclusions can be drawn. In conclusion, bronchoscopy is a useful tool in the diagnosis of bronchogenic cysts, both for confirmation of the cystic nature of the lesion by endobronchial ultrasonography and for confirmation of the diagnosis by TBNA (conventional or EBUS-guided depending on the expertise/comfort of the operator) of the cyst fluid. Therapeutic aspiration of the cyst can be considered as an alternative to surgery in adults with bronchogenic cysts of the mediastinum, especially in those unfit or reluctant for surgery. Whether therapeutic TBNA can be used as a primary modality for management of mediastinal bronchogenic cyst in all patients is debatable. Close monitoring is required to detect any recurrence of cyst in patients managed with TBNA alone.
5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16.
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