Bronchoscopy,surgery and radiation therapy for bronchial adenoid cystic carcinoma: A retrospective cohort study

Abstract

Background

Adenoid cystic carcinoma (ACC) of the bronchus is a rare malignancy, accounting for 1-2% of all respiratory tumors. Its slow growth often results in delayed diagnosis. Although surgical resection is the preferred treatment, ACC frequently demonstrates local invasiveness, leading to central airway obstruction that worsens respiratory symptoms and adversely affects prognosis. Consequently, bronchoscopic interventions and radiation therapy are often required for disease management.

Objective

To evaluate the long-term outcomes of multimodal management, including surgery, radiation therapy, and bronchoscopic interventions, in patients with bronchial ACC treated at our institution.

Methods

We conducted a retrospective review of medical records for patients diagnosed with bronchial ACC at our institution between April 1, 2005, and December 31, 2024. Clinical data, including patient demographics, treatment modalities, and overall survival (OS), were collected and analyzed.

Results

Eleven patients with central airway lesions were included. The mean age at diagnosis was 61±15 years, and the median OS was 73.4 months (range: 1-158 months). Bronchoscopic interventions under general anesthesia, including argon plasma coagulation, high-frequency snaring, and airway stenting, were performed in nine patients. Seven patients underwent surgical resection, including six tracheal anastomoses and one left total pneumonectomy. Postoperative radiation therapy was administered to seven patients.

Conclusion

A multimodal approach incorporating bronchoscopy, surgery, and radiation therapy may improve outcomes in patients with bronchial ACC.

Keywords

adenoid cystic carcinoma airway stenting argon plasma coagulation high-frequency snare radiation therapy surgery

Introduction

Adenoid cystic carcinoma (ACC) is a relatively rare malignant tumor arising from secretory gland tissue. According to the World Health Organization (WHO) classification, ACC of the lung is categorized among salivary gland-type tumors. It is a biphasic neoplasm composed of epithelial and myoepithelial cells. ACC accounts for approximately 1-2% of all head and neck cancers and about 10% of salivary gland tumors; however, it can also occur in other gland-bearing organs, including the airways.¹

Among salivary gland-type tumors of the bronchial tree, ACC is considered the third most common overall, following mucoepidermoid carcinoma. However, ACC shows a higher incidence in the trachea and main bronchi, whereas mucoepidermoid carcinoma typically arises more peripherally. Therefore, ACC is regarded as the second most common tumor of the trachea.^2–5

Metastatic disease occurs in 18% - 70% of cases.⁶ Hematogenous spread is more common, with the lungs representing the most frequent site of distal metastasis. Regional lymph node involvement is less common (10% - 19%) but is associated with a poorer prognosis.

Bronchial ACC typically progresses insidiously and is slow growing. Symptoms include dyspnea, chronic cough, wheezing, asthma-like presentations, and hemoptysis. Because of these features, the disease is sometimes misdiagnosed as asthma or chronic obstructive pulmonary disease (COPD). At the time of diagnosis, many cases are already locally advanced, with extensive infiltration and distant metastasis.

Despite its slow growth, bronchial ACC often demonstrates perineural invasion, local recurrence, and eventual distant spread. Reported survival rates after resection range from 52% to 95% at 5 years and 29% to 81% at 10 years.^7–11 Patients with incomplete resections or unresectable tumors have substantially worse outcomes compared to those who achieve complete resection.

Surgical resection remains the primary treatment. However, radiation therapy and bronchoscopic interventions are important options when complete resection is not feasible. Bronchoscopic therapy can achieve immediate airway patency rates exceeding 95% and may serve as a bridge to surgery or radiation. Given the rarity of bronchial ACC and the limited number of published reports, we conducted this study to evaluate the long-term outcomes of multimodal interventions at our institution.

Materials and Methods

We conducted a retrospective review of medical records from 11 patients diagnosed with bronchial ACC who presented at St. Marianna University School of Medicine between April 1, 2005, and December 31, 2024. Patients younger than 18 years, pregnant women, and those who declined participation were excluded.

All patients received one or more treatments, including bronchoscopic interventions (argon plasma coagulation (APC), high-frequency snaring, and stenting under rigid bronchoscopy), radiation therapy, and surgery. Clinical data, including demographics, treatment modalities, and overall survival (OS), were collected. The primary endpoint was OS.

Statistical analysis was performed out using JMP 18.22 (SAS Institution, Cary, NC, USA). Survival rates were estimated using the Kaplan–Meier method.

Patients were informed about the study and given the opportunity to opt out of participation. The study protocol was approved by the institutional ethics committee (Approval Number: 6730). The reporting of this study conforms to the STROBE statement⁸ (Supplemental file 1).

Results

Eleven patients with central airway lesions were included in the study (nine tracheal, one right main bronchus, and one left main bronchus). The mean age at diagnosis was 61±15 years, and the median OS was 80.6 months (range: 1-158 months). A summary of patient characteristics is presented in Table 1. The primary tumor site was the airway in all cases.

Table 1.

Patient characteristics and outcomes.

Case	Age	Sex	Location	Size (mm)	Stenosis rate at diagnosis	Primary treatment	Radiation dose	Prognosis
1	44	M	Trachea	15 x 16 x 21	80%	Tracheal coronectomy	60 Gy/30 fr	Death
2	78	F	Trachea	20 x 20 x 19	60%	Bronchoscopic intervention	–	Death
3	52	F	Trachea	10 x 15 x 13	60%	Tracheal coronectomy	60 Gy/30 fr	Death
4	50	M	Trachea	9 x 17 x 14	40%	Tracheal coronectomy	60 Gy/30 fr	Survival
5	61	F	Trachea	12 x 12 x 13	40%	Bronchoscopic intervention	–	Survival
6	79	M	Trachea	11 x 11 x 11	30%	Tracheal coronectomy	–	Transfer
7	36	F	Trachea	12 x 14 x 18	60%	Tracheal coronectomy	60 Gy/30 fr	Survival
8	65	M	Trachea	9 x 15 x 13	60%	Tracheal coronectomy	60 Gy/30 fr	Transfer
9	74	M	Right main bronchus	10 x 14 x 21	95%	Bronchoscopic intervention	66 Gy/33 fr	Survival
10	55	F	Left main bronchus	Unmeasurable	100%	Left total pneumonectomy	60 Gy/30 fr	Survival
11	81	M	Trachea	13 x 19 x 25	40%	Bronchoscopic intervention	–	Transfer

Bronchoscopic intervention under general anesthesia, including APC and high-frequency snaring, were performed in nine patients. Four patients required multiple bronchoscopic procedures. In cases where an AERO stent (Merit Medical Systems, South Jordan, USA) was implanted, complications such as sputum retention and empyema were observed. In all cases, bronchoscopic intervention was used as a first-line approach to relieve airway and obtain definitive diagnosis (Cases 2,3,4,7,9,10). Secondary interventions were performed for postoperative restenosis after tracheal coronectomy (Case 3) and for recurrent symptoms after initial bronchoscopic treatment (Cases 2 and 6).

Surgical resection was performed in seven patients, consisting of six tracheal anastomoses and one left total pneumonectomy. Case 1 underwent surgery at another hospital. Postoperative radiation therapy (60–66 Gy in 30–33 fractions) was administered to five patients. In the pneumonectomy case, radiation therapy was added because of positive resection margins (Table 2).

Table 2.

Bronchoscopic interventions, surgical procedures, adjuvant therapy, and outcomes.

Case	Bronchoscopic procedures	Timing of bronchoscopic procedures	Cause of death/Complications	Distant metastasis	Time from diagnosis (months)	VATS for pulmonary metastasis	Overall survival (months)
1	1. APC,	Recurrent (80 m, 93 m)	Stent-related difficulty expectorating, empyema	Lung	93	–-	103
1	2. APC + AERO stent	Recurrent (80 m, 93 m)	Stent-related difficulty expectorating, empyema	Lung	93	–-	103
2	1-5. High-frequency Snare + APC	Before diagnosis; recurrent (51 m,62 m,73 m,81 m)	Respiratory failure	Lung, bone, liver	95	-	97
3	1-2. High-frequency snare	Before diagnosis; recurrent (105 m)	Respiratory failure	Lung	10	-	112
4	High-frequency snare + APC	Before diagnosis	–	Lung	75	+	88
5	High-frequency Snare + APC	After diagnosis	–	–	–	–	84
6	1-2. APC	Before diagnosis; recurrent (12 m)	–	–	–	–	71
7	–	–	–	Lung	139	+	158
8	–	–	–	Lung	61	+	100
9	APC	Before diagnosis	–	Lung	10	-	50
10	APC	Before diagnosis	–	Lung	5	-	23
11	APC	After diagnosis	–	–	–	–	1

Abbreviations: APC = argon plasma coagulation; VATS = video-assisted thoracoscopic surgery.

During follow-up, pulmonary metastases developed in eight patients at a mean of 51 months after definitive diagnosis (range: 5–139 months). Video-assisted thoracoscopic surgery (VATS) was performed for pulmonary metastases in three of these cases.

Discussion

Our institutional experience with bronchial ACC indicates that surgery alone rarely achieves durable local control. However, the addition of radiation therapy and bronchoscopic interventions produced outcomes comparable to previously reported survival rates. The standard treatment for ACC remains surgical resection, involving removal of the affected tracheal or bronchial segment with airway reconstruction. Reported survival rates for resectable bronchial ACC range from 52% - 95% at 5 years and 29% - 81% at 10 years.^7–11 Incomplete or unresectable cases are associated with inferior outcomes. Achieving negative margins is therefore critical, but the high frequency of submucosal extension underscores the need for postoperative adjuvant therapy, including radiation therapy and bronchoscopic intervention (Figure 1).

Figure 1.

Bronchoscopic findings in representative cases. Case 1: (a, b) before and after argon plasma coagulation and high-frequency snaring. Case 2: (c) Immediately after AERO stent implantation; (d) six months after stenting. Case 3: (e) bronchoscopic intervention combined with postoperative radiation therapy; (f) severe tracheal stenosis due to recurrence approximately nine years after surgery.

Regarding prognostic factors, poor prognosis in thoracic ACC are associated with advanced stage at diagnosis, positive surgical margins, older patient age, and a solid histological growth pattern. While surgical resection remains the cornerstone of treatment, lymphadenectomy may be considered to assess nodal involvement.

Systemic therapy is palliative and is reserved for symptomatic or rapidly progressive disease that is not amenable to surgery or radiation therapy.^4,12 In treatment-naive patients, chemotherapy has demonstrated superior outcomes compared with tyrosine kinase inhibitors (TKIs), with a reported median overall survival of 48 months versus 18.7 months. Single-agent mitoxantrone, vinorelbine, or epirubicin are commonly used first-line options due to their favorable toxicity profiles and ability to achieve disease stabilization.

Despite high c-kit expression in ACC, c-kit inhibitors such as imatinib have shown minimal objective response. Multi-target TKIs (e.g., lenvatinib) rarely induce tumor shrinkage but may provide meaningful disease control. Immunotherapy has generally demonstrated limited efficacy, likely due to the immunosuppressive tumor microenvironment, and is currently restricted to selected patients with high tumor mutational burden (TMB-H) or microsatellite instability (MSI-H).

Bronchoscopic intervention serves multiple roles in the management of bronchial ACC. It enables diagnostic biopsy for histopathological confirmation, provides relief of airway obstruction, and can act as a bridge to surgery or radiation. It is also useful as a palliative option for recurrent symptoms after definitive treatment. Modalities include laser therapy, electrocautery (APC, high-frequency snaring), and microwave therapy. APC, snaring, and microwave ablation can be repeated, when necessary, whereas airway stenting is generally reserved for patients with shorter recurrence intervals. Cryotherapy may also be employed, although long-term control with this modality is often difficult to achieve. Tracheal and bronchial ACC are known to develop lung metastases at a high rate over extended follow-up. According to a report by Gu et al., distant metastasis at diagnosis occurred in 9.1% of tracheal ACC and 21% in lung ACC, with surgery and radiotherapy serving as the primary treatment modalities.^13,14 Our results suggest that the addition of bronchoscopic therapy may further contribute to long-term disease control. For elderly patients, in whom surgery may not be feasible, radiotherapy combined with bronchoscopic intervention may represent an effective alternative treatment approach.

Airway stenting is primarily a palliative measure in cases of restenosis after surgery or radiation, particularly when bronchoscopic procedures must be repeated within short intervals. Currently available stents include silicone, metal, and hybrid types. Metal stents are often chosen for short-term symptom relief, while silicone and hybrid stents are preferred when longer survival is anticipated. Stent-related complications, such as impaired expectoration, granulation tissue formation, tumor overgrowth, migration, and infection, are almost inevitable with long-term use, making careful patient selection essential. Recently, case reports have highlighted the potential utility of photodynamic therapy (PDT).^15–17 PDT is a minimally invasive technique in which a photosensitizing drug, when activated by light of a specific wavelength, generates reactive oxygen species that destroy tumor cells. Although encouraging, current evidence is limited to small series, and multicenter studies are needed given the rarity of the disease.

Complete resection and negative margins remain the most important determinant of long-term survival. However, submucosal and perineural invasion contribute to the frequent occurrence of positive margins, even when surgery appears macroscopically complete.^9,10 Adjuvant therapy, particularly external beam radiation therapy (EBRT), should therefore be considered. A total dose of 60 Gy or more is recommended for airway lesions, consistent with the regimen administered at our institution.¹ Proton beam therapy and carbon ion radiotherapy have also been reported to provide outcomes comparable to EBRT and represent additional treatments options.¹⁸

This study has several limitations. As a retrospective review of a rare tumor, the availability and completeness of clinical information varied across cases, and certain details, such as macroscopic tumor extension, length of airway resection, and some procedural parameters, were not consistently documented. The cohort was heterogeneous in terms of treatment intent, reflecting real-world clinical decision-making in a disease with no standardized management pathway. In addition, several patients were transferred to outside hospitals, which limited the completeness of follow-up. Given the small sample size, these findings should be interpreted descriptively rather than as definitive evidence to guide treatment.

Despite these limitations, advances in surgical techniques, bronchoscopic modalities, and radiation therapy are expected to improve outcomes for bronchial ACC. Moreover, the development of molecular-targeted agents and immunotherapies may expand treatment options for advanced cases in the future.

Conclusion

ACC is often advanced at diagnosis and carries a high rate of pulmonary metastasis even after surgical resection. In older patients or those who are not surgical candidates, bronchoscopic therapy may be a reasonable first-line option. Radiotherapy can be safely combined with either approach and serves as a useful adjunctive treatment.

Supplemental material

Supplemental material - Bronchoscopy, surgery and radiation therapy for bronchial adenoid cystic carcinoma: A retrospective cohort study

Supplemental material for Bronchoscopy, surgery and radiation therapy for bronchial adenoid cystic carcinoma: A retrospective cohort study by Hiroshi Handa, Yu Numata, Kazuhiro Nishiyama, Hajime Tsuruoka, Kei Morikawa, Takeo Inoue and Masamichi Mineshita in Rare Tumors

Footnotes

Acknowledgments

The authors thank Mr. Jason Tonge from St. Marianna University School of Medicine for the linguistic review of this manuscript.

ORCID iDs

Hiroshi Handa

Kazuhiro Nishiyama

Kei Morikawa

Ethical considerations

The study protocol was approved by the ethics committee at St. Marianna University School of Medicine (Approval Number: 6730). The study was conducted in accordance with the Declaration of Helsinki.

Consent to participate

Participants were informed about the study and given the opportunity to opt out. The requirement for written informed consent was waived by the ethics committee.

Consent for publication

An opt-out procedure for publication was approved by the institutional ethics committee.

Author contributions

H. H. had full access to data in this study and takes responsibility for the integrity and accuracy of data analysis. Y.N., K.N., H.T, K.M., T.I., and M.M. contributed to the scientific review and final approval of this manuscript. All authors read and approved the final manuscript.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Data Availability Statement

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.*

Supplemental material

Supplemental material for this article is available online.

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