Efficacy of bronchoscopic therapies for bronchial mucoepidermoid carcinoma in children: results from six patients


Aims and Background

Bronchial mucoepidermoid carcinoma is a rare disease in children, and lobectomy is traditionally considered as a first-line treatment. As the tumor is characterized by intraluminal growth, low malignancy and superficial infiltration of bronchial walls, bronchoscopic interventional therapy may provide an alternative treatment with favorable results. The aim of the study was to evaluate the efficacy and safety of bronchoscopic therapies for bronchial mucoepidermoid carcinoma in children.

Methods and Study design

Clinical manifestations, multiple bronchoscopic interventions and outcomes in 6 children with bronchial mucoepidermoid carcinoma were retrospectively analyzed.


The median age was 8.7 years (range 4 to 12 years). All the tumors were located in the lobar bronchus and were detected by computerized tomography. Diagnoses of low-grade mucoepidermoid carcinoma were made based on biopsies obtained via bronchoscopy. Five tumors were classified as intraluminal type and successfully eradicated by carbon dioxide cryotherapy and argon plasma coagulation under bronchoscopy. The other tumor in patient 3 was classified as the mixture type and could not be removed by a bronchoscopic, so left upper lobectomy was performed. For each patient, interventional procedures were conducted on the average for 6 times. No recurrence was detected by bronchoscopic inspections or computed tomography scans during follow-ups for 16-72 months.


Multiple bronchoscopic procedures, as alternative treatments, are effective in removing bronchial mucoepidermoid carcinoma mucoepidermoid carcinoma in children without any major complications.

Tumori 2015; 101(1): 52 - 56




Hongwu Wang, Jieli Zhang, Dongmei Li, Nan Zhang, Jing Li, Jiangfeng Mao

Article History


Financial support: No financial support was received for this submission.
Conflict of interest: The authors have no conflict of interest.

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Mucoepidermoid carcinoma (MEC), derived from salivary mucus glands, usually occurs in the parotid and submandibular salivary glands. Bronchial MEC is very rare in adults, accounting for 0.2% of all primary lung cancers and 2.5-7.3% of all bronchial tumors (1, 2). However, in children, it comprises 30-70% of all bronchial tumors (1, 3). The tumor is usually characterized by intraluminal growth, low-grade malignancy and superficial infiltration of bronchial walls. In pathology, MEC is classified into high-grade and low-grade types according to histological features, including nuclear pleomorphism, mitotic activity and necrosis. Low-grade MEC is comprised predominantly of glandular elements and mucin-secreting cells, whereas high-grade MEC consists largely of sheets of squamoid and intermediate cells intermixed with smaller populations of mucus-secreting cells. Necrosis and mitosis appears only in the high-grade MEC (4). Patients with low-grade MEC have a much better prognosis than those with high-grade MEC (2).

Molecular studies in salivary and pulmonary MECs have shown that nearly 80% of bronchial MEC harbored a CRTC1-MAML2 fusion protein (5). This novel fusion protein is generated by translocation of chromosome (11; 19). It may disrupt normal cell cycle control and cellular differentiation, resulting in tumor formation (6). It has been confirmed that tumors harboring the CRTC1-MAML2 fusion protein had a favorable prognosis regardless of pathological type (5, 6).

Lobectomy or sleeve resection of the involved bronchus is the first-line treatment for the disease, and 10-year survival is near 90% (3, 7-8-9). Bronchoscopy was used mainly for inspection and biopsy, seldom for therapeutic purposes (8). Therefore, the efficacy of bronchoscopic interventions in treating MEC is largely unknown. The aim of the study was to evaluate the efficacy and side effects of bronchial therapies in 6 children with bronchial MEC.

Patients and Methods

Patient selection

Six children with bronchial MEC, admitted to our hospital between July, 2008, and December, 2012, were included in the study. Diagnoses were made from samples obtained via bronchoscopic biopsy in our hospital. Bronchoscopic interventional procedures were conducted for each patient as the main treatments. Written informed consents were obtained from the parents of each patient. The study was approved by the ethics committee of the China Meitan General Hospital.

Therapeutic methods

Preoperative preparations

Routine blood tests, electrocardiogram, blood gas analysis, pulmonary function tests, chest X-rays and computed tomography (CT) scans were examined before treatments. Preoperative assessments and anesthesia assessments were performed by anesthesiologists and pulmonologists. The movements of the mouth, teeth, jaw bones and neck were carefully examined.

General anesthesia, anesthesia induction, and maintenance

All patients underwent general anesthesia for bronchoscopic interventions. Oxygen was given by a face mask for 5 to 10 min before anesthesia. Either 0.5 mg atropine or 0.3 mg hyoscine was administered intravenously 10 min before procedures to inhibit excessive secretions in the airway. Blood oxygen saturation, electrocardiogram, blood pressure readings and respiratory movements were monitored throughout the procedures.

Anesthesia induction and maintenance were performed as follows. Midazolam (an anti-anxiety and anti-amnesic drug), 2 mg, was intravenously administered 5 min before the anesthesia. Subsequently, fentanyl (1-2 μg/kg) and 1% propofol (1-2 mg/kg body weight) were intravenously administered. Skelaxin atracurium (0.5 mg/kg) was then administered. A rigid bronchoscope was inserted when muscle trembling disappeared and the muscles in the lower mandible were relaxed. The patients’ eyes and teeth were protected during general anesthesia. Propofol and remifentanil were used for the maintenance of anesthesia.

Insertion of a rigid bronchoscope

Three patients underwent electronic flexible bronchoscopy and the other three underwent rigid bronchoscopy. The rigid bronchoscope, 6.0~8.5 mm diameter, was from Karl Storz (Karl Storz GmbH & Co., Tulingen, Germany). The patient was required to lie in a supine position with a cushion under his shoulder. Under the guidance of an indirect laryngoscope or direct vision, the rigid bronchoscopy was inserted into the trachea.

Bronchoscopic interventional procedures

Argon plasma coagulation and dioxide carbon cryotherapy were applied to remove the tumors in the main trachea under the guidance of the rigid instrument. For tumors in the bronchus, an electronic flexible bronchoscope (PENTAX-EPM 3500, Pentax Ricoh Imaging Co, Tokyo, Japan) and other procedures were used.

A Cesel type 3000 instrument (Soring GmBH, Quickborn, Germany) was used for argon plasma coagulation. The mass could be cauterized by the argon plasma coagulation probes with an output power of 30-50 W and an argon flow rate of 0.8/min. Inhalation of oxygen during the cauterization was to be maintained. The remaining coagulated tissues were removed by biopsy forceps.

Carbon dioxide cryotherapy was performed by using a freezing therapeutic instrument (ERBE Co., Tubingen, Germany). The cryo-probe was 1.5 mm in diameter and 5 mm in terminal length. The cryogen was liquid carbon dioxide. The freezing probe was placed on the surface or into the tumor for 5-10 s, generating an ice ball surrounding the probe. Then, the crystallized tumor tissue was removed from the surface of the airway. Such a procedure can be repeated several times until tumors in lumen surface are completely removed. When hemorrhage occurred, argon plasma coagulation was used to stop the bleeding.

Efficacy evaluation

The response to treatment was assessed by the followings criteria. Complete remission: the mass has been completely removed from the airway. Partial remission: the recanalized area is over 50% of the airway and the apnea symptom has significantly improved. Minor remission: the recanalized area is less than 50% of the airway, but distal obstructive pneumonia has been resolved due to the drainage. No remission: the mass could not be removed and no remission was achieved. The severity of dyspnea was scored by the American Thoracic Society dyspnea scale, and the general physical status was evaluated by the Karnofsky scoring system.


After initial endoscopic procedures, chest CT scans and bronchoscopic inspections were performed at an interval of 2 to 3 months. Tumor recurrence revealed by CT or bronchoscopy would be treated by endoscopic procedures. The last follow-up was completed by December, 2013.

Statistical analysis

Student’s t test was used to compare changes in the ­Karnofsky score, and the American Thoracic Society dyspnea scale was used before and after interventional procedures. Quantitative data were expressed as means ± standard deviation. P<0.05 was defined as statistically significant.


General information

There were 5 boys and one girl. The average age was 8.7 years (range 4 to 12 years). Cough, productive sputum and fever were the major complaints. Hemoptysis occurred in two patients. The duration between initial symptoms and final diagnosis was 13 ± 4.7 months (range 6 to 36 months). Pneumonia was diagnosed in 4 patients and pulmonary tuberculosis in the other 2 patients before the pathological diagnosis was made. Antibiotics and anti-tuberculosis therapies had been used, with no improvement. In our hospital, the pathology obtained by bronchoscopy revealed low-grade MEC.

Tumor locations

Four tumors located in the opening of the lobar bronchus and the other two located in the opening of the segmental bronchus (details in Tab. I). The masses and the atelectasis of involved segments could be detected in chest CT scans. On CT images, 5 patients presented with intraluminal well-circumscribed nodules. In patient 3, the mass extended into the pulmonary parenchyma.

Clinical features and treatments in 6 children with low-grade bronchial mucoepidermoid carcinoma

No. Gender Age (yr) Tumor location Bronchoscopy findings Bronchoscopic interventions & follow-up
Lt = left; Rt = right; LB = lobar bronchus.
1 M 4 Lt lower LB A polypoid partially obstructing the lumen Cleared; no recurrence after 72 mo
2 M 7 Rt middle LB A polypoid blocking the lumen Cleared; no recurrence after 48 mo
3 F 10 Lt upper division LB A polypoid blocking the lumen Failure to recanalize the lumen by endoscopy therapy; resection of the involved segment; no recurrence after 24 mo
4 M 12 Rt middle LB Covered with white necrotic material, blocking the lumen Cleared; no recurrence after 18 mo
5 M 10 Lt low LB Covered with white necrotic materials blocking the lumen Cleared; no recurrence after 18 mo
6 M 9 Lt upper division LB A mass similar to a cauliflower blocking the lumen Cleared; no recurrence after 16 mo

Findings and treatments by bronchoscopy

On the average, bronchoscopic interventional procedures were performed 6 times in each patient. Rigid bronchoscopy was conducted in 3 patients, soft bronchoscopy in 1 patient, and a laryngeal mask in 2 patients. Grossly, three tumors appeared polypoid (see Fig. 1), two were covered with massive necrosis, and one was shaped like a cauliflower. Five intraluminal tumors were successfully removed by carbon dioxide cryotherapy and argon plasma coagulation under bronchoscopy. In patient 3, the tumor failed to be cleared by bronchoscopic therapy. A left upper lobectomy was then conducted, and the tumor was completely resected.

Bronchoscopic findings, pathology and follow-up in a 7-year-old boy (patient no. 2). The patient presented with intermittent cough and fever for one year. Endoscopic inspection revealed a polypoid mass obstructing the right middle lobar bronchus (A). Pathology showed a combination of epidermoid cells, mucus-secreting cells and intermediate cells (200×), indicating a diagnosis of low-grade mucoepidermoid carcinoma (B). The tumor was completely removed, and the bronchus was recanalized after multiple bronchoscopic interventions: carbon dioxide cryotherapy 4 times and argon plasma coagulation twice (C). The repeated endoscopic inspection showed a smooth orifice in the right middle lobar bronchus at 48 months after bronchoscopic therapy (D).

The Karnofsky score increased from 78.3 ± 1.7 to 90 ± 2.6 (p<0.01) and the American Thoracic Society dyspnea scale increased from 2.0 ± 0.2 to 1.0 ± 0.2 (p<0.01) after the first endoscopic procedure.


No patient died due to bronchoscopic interventions. The rigid bronchoscopic procedures led to glottis edema in one patient, which was quickly alleviated by intravenous glucocorticoids. No other significant complications were observed.


For 5 patients treated by endoscopic procedures, no relapse was detected by CT scans during 16-72 months of follow-up. For patient 3, left upper lobectomy was performed, and no relapse was detected during 24 months of follow-up.


We evaluated 6 children with MEC primarily treated by bronchoscopic interventional therapies. The tumors were successfully removed in 5 patients, whereas for patient 3, the tumor was resected by lobectomy. Pathologically they were low-grade MEC. No recurrence was detected during follow-up periods of 16-72 months. To our knowledge, this is the first study focusing on evaluation of bronchoscopic interventions as dominant treatments in pediatric bronchial MEC, and the results are promising.

According to the definition of WHO, MEC is a low malignant potential epithelial tumor, characterized by a combination of epidermoid cells, mucus-secreting cells and intermediate cells (10). The tumor is classified as low-grade or high-grade on pathology. The prognosis is usually good, and the 10-year survival rate is near 100% for low-grade MEC after lobectomy (2, 4, 11), whereas for high-grade MEC, the disease will progress even after surgery (2, 11). All 7 patients with high-grade MEC relapsed after the operations, and 4 of them died within a 2-year follow-up (2).

In adults, nearly 20% of bronchial MEC are high-grade (2, 12), whereas in pediatric patients, few high-grade bronchial MEC have been reported (8, 13-14-15-16-17). In our study, all patients had low-grade MEC on pathology, which is consistent with previous reports. Considering that the low-grade MEC had a tendency of low malignancy, indolent progression and superficial location on a bronchus, it seemed possible and rational to remove the mass by several bronchoscopic interventional therapies.

As regards the location of bronchial MEC, 40% of MEC occurs in the trachea and 60% in the proximal part of the lobar and segmental bronchus (2). The growth of low-grade MEC is restricted to the intra-lumen and rarely invades surrounding tissues (2, 12). CT scan can reveal an intraluminal mass, obstructive pneumonia, lobar and segmental atelectasis, middle lobe syndrome, and pleural effusion (12). Intraluminal nodules usually present as ovoid with clear margins (12, 18). They can be slightly or moderately enhanced by contrast agents (12). In our study, all tumors could be clearly identified in the orifices of lobar or segmental bronchus by chest CT images. Bronchoscopy interventional procedures could be performed perfectly in the trachea and bronchus.

Progressive obstruction of the airways may cause recurrent pneumonia, cough, hemoptysis, dyspnea, and fever. However, the diagnosis of MEC is usually delayed because such symptoms are nonspecific (13). In our study, the diagnosis was delayed by 6 to 40 months, which suggests that timely chest CT scans or bronchoscopic inspections may help to establish the diagnosis earlier.

Lobectomy or sleeve resection of the involved bronchus seems to be the only way to cure the disease, since the tumor is resistant to radiotherapy and chemotherapy. Even though the purpose of surgery is to remove the tumor with the sacrifice of as little normal lung tissue as possible, the risks of thoracic deformity and partial loss of pulmonary function are still unavoidable. Bronchoscopic therapy may avoid these risks and completely normalize pulmonary function.

In our study, bronchoscopic interventional procedures, as a primary treatment, were performed in 6 pediatric patients. The tumors were completely eradicated by carbon dioxide cryotherapy and argon plasma coagulation in 5 patients and no recurrence occurred during the follow up. Polypoid tumors on the surface of bronchial wall could be crystallized and removed by dioxide carbon. Cauterization of the lesion by argon plasma may further destroy the tumor residue and stop bleeding. After the tumor was removed by bronchoscopic procedures, regular endoscopic inspection and chest CT are necessary. If a tumor is invading the bronchial wall or a relapse occurs, lobectomy could be conducted at any time when necessary.

Bronchoscopic therapy in bronchial low-grade MEC has several advantages. First, the obstructed bronchus can be quickly recanalized, accompanied by a significant relief of symptoms. Second, the low-malignant-potential tumor is superficially derived from the bronchus and can be completely eradicated by bronchoscopic interventions. Last but not least, pulmonary function is totally preserved. Minimal invasive procedures can be performed repeatedly if required, and complication is rare.

In patients with bronchial high-grade MEC, surgery is strongly recommended as the main treatment. In this scenario, bronchoscopic intervention may help to reopen the airway and improve the life quality. Tyrosine kinase inhibitors may have some beneficial effects on the patients (19-20-21). A fused oncogenic protein, CRTC1-MAML2, was identified in more than 50% of bronchial MEC and may partially account for the response to treatment with tyrosine kinase inhibitors (22, 23).

Our study had some limitations. First, the sample size is small and the follow-up time is not long enough. However, 6 patients is a relatively large number due to the rarity of the disease. Most of the patients have been described in case reports. The follow-up will continue in our hospital. Second, as a retrospective observational study, no control groups were included. More prospective and multicentric studies are required to further clarify the beneficial effects of bronchoscopic therapy. Last, the conclusions from the study cannot be extrapolated to adult patients. The higher incidence (20%) of high-grade bronchial MEC in adults makes the eradication of tumors by endoscopic procedures difficult.

In summary, our study shows, for the first time, that bronchoscopic therapy is highly effective in eradicating bronchial low-grade MEC in children. The minimal invasive procedures may recanalize the bronchus and restore pulmonary function without significant complications. More prospective studies with larger sample size and longer follow-up are required to further confirm this conclusion.


Financial support: No financial support was received for this submission.
Conflict of interest: The authors have no conflict of interest.
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  • Department of Medical Oncology, China Meitan General Hospital, Beijing - PR China
  • Endocrinology Department, Peking Union Medical College Hospital, Beijing - PR China

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