Primary tracheo‐bronchial adenoid cystic carcinoma: A surgical series with literature review

Abstract

Tracheo‐bronchial adenoid cystic carcinoma (TBACC) is a rare disease. Its treatment is mainly surgical. We herein describe the clinical and para‐clinical varieties of TBACC as well as their surgical treatment and prognosis. We conducted a retrospective study of eight patients operated on between 1994 and 2022 and whose definitive pathological examination concluded with primary TBACC. There were three men and five women with an average age of 44 years. The bronchoscopy found a budding formation reducing the tracheal lumen at the cervical (two cases), middle (two case) and distal trachea and carina (four cases). Bronchial anastomosis resection and sleeve pneumonectomy were the most common procedures. Surgical resections R0 were achieved in five patients. Surgery followed by adjuvant radiotherapy was performed in two patients with incomplete surgical resection R1. The overall survival for all patients with primary ACC was 72% at 5 years. TBACC is a rare and low‐to‐moderate grade malignant tumour. The choice of the surgical procedure and the appropriate approach is challenging to obtain a promising prognosis.

Curative treatment of TBACC is a real challenge. Complex resection is associated with high postoperative morbidity and mortality rates. When complete resection is not achieved, incomplete resection with adjuvant treatments would also provide a promising prognosis.

INTRODUCTION

Primary malignant tumours of the trachea and bronchus are rare. Adenoid cystic carcinoma (ACC) is the second most common tumour of trachea after squamous cell carcinomas. ¹ , ² It is usually consigned as a non‐small cell lung carcinoma. It generally occurs around the 4th–5th decade with no predominance of gender or relation to tobacco. ³ It arises from the submucosal layer and is characterized by slow growth and unpredictable clinical course. It is often diagnosed at a relatively advanced stage. Since the clinical behaviour of these tumours is different from the conventional lung tumours, it is important to accurately diagnose them. Hemoptysis, nonproductive cough, dyspnea and chest pain are the frequent early manifestations. ⁴

Surgical resection with airway reconstruction is the main treatment for tracheo‐bronchia ACC(TBACC) with a possible role for adjuvant radiotherapy.

Due to the rareness of ACC, very little data has been published. Their optimal treatment strategy is still controversial. It has good prognosis, if diagnosed and treated at the right time.

We retrospectively searched the information database of 11 cases with TBACC operated in our department between January 1st 1994 and 31st December 2022. Eight cases of primary TBACC were collected. Two patients with secondary adenoid cystic carcinoma and one other with an advanced tumour requiring a diagnostic biopsy were excluded. Demographic characteristics, pathological and clinical features, multimodality treatments and survival outcomes were recorded.

Follow‐up data were obtained by contacting the patients (telephone calls). All patients were reviewed periodically at the outpatient clinic postoperatively at 1 month, 3 months then every 6 months for 2 years then annually for 5 years.

CASES SERIES

A total of eight patients with histologically confirmed TBACC were included in this study. There were five females and three males with a median age of 41 years [27–54]. Five patients were smokers, and 1 had a history of breast neoplasia.

Dyspnea (n = 4) and non‐productive cough (n = 4) were the most frequent complaints, followed by wheezing (n = 2), dysphagia (n = 1) and small hemoptysis (n = 1). The duration of symptoms ranged from 6 to 24 months (average = 17 months). Seven patients exhibited more than one symptom. All patients were evaluated with a standard chest x‐ray, chest computed tomography scan and bronchoscopy. A budding formation reducing the tracheal lumen at the cervical (n = 2), middle (n = 2) and distal trachea and carina (n = 4) was found at the bronchoscopy. Figure 1D,E shows a bronchoscopy of case 8 finding an obstructive red bud of the LMB, hyper vascularized with carinal involvement. Bronchial biopsies led to a diagnosis of ACC in all cases.

FIGURE 1.

(A, B): Computed tomography chest scan with contrast administration in axial (B) and frontal (C) view. Tumoral mass marked with a white arrow completely obstructing the lumen of the left main bronchus with exobronchial extension, leading to a left pulmonary collapse (case 8). (C): Chest MRI in T1 WI after Gadolinium administration showing the endobronchial mass with mediastinal extension and left pulmonary collapse (case 8). (D, E): Endoscopic features of tracheo‐bronchial adenoid cystic carcinoma (TBACC): A bronchoscopy finding an obstructive red bud of the LMB, hyper vascularized with carinal involvement (case 8). (F, G): Operative views of TBACC: Terminal anastomosis resection between the RMB and the trachea 2 cm from the carina was performed. A left pneumonectomy with carinal resection widened to the bronchial axis had been completed. (F): Terminal anastomosis between the RMB and the trachea after left pneumonectomy with carinal. 1: Trachea; 2: Carina; 3: RMB; 4: Tumour invading the MLB. (G): The surgical piece showing the tumour invading the MLB and the carinal resection. 1: Trachea; 3: RMB; 5: Right lung; White arrow: Terminal anastomosis resection between the RMB and the trachea. (H–J): Anatomo‐pathological features of TBACC: (H): Low power micrograph (H&E, 4× magnification) showing a tubular pattern and nested pattern. (I): Medium power micrograph (H&E, 10× magnification) showing a compact sheet‐like and nested pattern of rounded basaloid cells. Tumour stroma exhibited myxoid characteristics. (J): High power micrograph (H&E, 40× magnification) showing small myoepithelial cells with bland cytology surrounding pseudoglandular spaces filled with mucin and basement membrane material.

The CT scan found in six patients an endo‐luminal tracheal tissue process specifying its longitudinal length, annular wall thickening, transmural growth, poorly defined border and mild enhancement.

For one patient (case 8), the tumour obstructed the left main bronchus with extension to the carina and thoracic trachea (Figure 1A,B). The median tumour size was 3.3 ± 2 cm.

Thoracic magnetic resonance imaging (MRI) (Figure 1C of case 8) (n = 6) and oesogastro duodenal transit (n = 1) were performed for suspicion of oesophageal involvement and concluded that there were no lesions. There was no distant metastasis in the assessment of extension.

The preoperative diagnosis of ACC was retained in two patients on bronchial biopsies. All cases were discussed in a multidisciplinary conference concluding the surgical resection. The procedures performed were tracheal anastomosis resection (n = 4), left pneumonectomy extended to the carina and trachea (n = 2) (Figure 1), lobectomy (n = 1), and exploratory thoracotomy (n = 1). The anatomopathological examination concluded to the intraluminal growth pattern as the most frequently encountered (n = 3), followed by whole‐wall infiltration (n = 2) and extraluminal growth (n = 2).

The mean hospital stay was 8 days (±3). The histological study showed a malignant epithelial proliferation arranged in cribriform and trabecular glandular structure filled with a mucoid substance (Figure 1). The overall mean resected tumour size and tracheal length was 31.62 ± 7 mm. The tumour stroma was fibro‐hyaline. Resections were classified as negative margins resection (R0) or microscopically margin‐positive resection (R1). There was no macroscopically margin‐positive resection (R2). Surgical margin was R0 in 5 patients and R1 in 2 patients. Furthermore, the histological study confirms the presence of pleural metastasis of TBACC for the patient having an exploratory thoracotomy.

The postoperative course was simple in all patients except one presenting right basal pneumonia with good progress under antibiotic therapy. One postoperative death related to multivisceral failure was noted (case 11 in Table 1).

TABLE 1.

Summary of cases.

No	Age (years)/sex	Clinical presentation/stage	Location	Tumour size	Approaches	Procedure	Postoperative complication	R0/R1/R2	Postoperative bronchoscopy	Radiotherapy	5‐year survival rate
1	54/F	Dyspnea Cough	Distal trachea and carina	12 mm	Left hemi Clamshell approach	Left pneumonectomy extended to carina and trachea	Multiorgan failure/death on day1	R0	–	–	–
2	53/F	Dyspnea Wheezing	Cervical trachea	35 mm	Cervicotomy	Tracheal anastomosis resection	0	R0	25% stenosis	Yes	Yes
3	51/F	Dyspnea Hemoptysis	Middle trachea	27 mm	Cervicotomy	Tracheal anastomosis resection	0	R0	Normal calibre	No	Yes
4	40/F	Cough	Right main bronchus	18 mm	Posterolateral thoracotomy	Exploratory thoracotomy	0	–	–	Yes	No
5	39/M	Dyspnea Cough	Distal trachea and carina	56 mm	Sternotomy	Tracheal anastomosis resection	0	R1	30% stenosis	Yes	No
6	37/F	Cough	Distal trachea and carina	21 mm	Posterolateral thoracotomy	Lobectomy	0	R0	–	No	Yes
7	27/F	Dyspnea Wheezing	Cervical trachea	32 mm	Cervicotomy	Tracheal anastomosis resection	0	R1	20% stenosis	Yes	Yes
8	30/M	Dyspnea Chest pain	Carina + left main bronchus	52 mm	Double lateral thoracotomy	Left sleeve pneumonectomy	Pneumonia	R0	Normal calibre	No	Yes

Abbreviations: F, female; M, male.

Postoperative bronchoscopy was undergone for all patients having a tracheal anastomosis resection (n = 4). It revealed a stenosis of around 37% opposite the anastomosis in 2 cases (R1 and R0) at the 6th and 12th postoperative month, respectively, and a tracheal suture without dehiscence and with normal calibre in the 2 other cases.

Multidisciplinary treatment including radiotherapy and chemotherapy were needed to obtain lower rates of local recurrence, distant metastases, and better prognosis. Survivor patients with an incomplete surgical resection R1 (n = 2) underwent adjuvant radiotherapy as a multi‐modal treatment approach.

Furthermore, one R0‐resected patient (12.5%) also received adjuvant radiotherapy because of a recurrence with anastomotic stenosis at 12th postoperative month (case 2). For the patient with pleural metastasis, radiotherapy and chemotherapy were undergone.

After a mean follow‐up of 5.7 years (range 5–8 years) for survivors (n = 7), 2 (28%) patients had died. Of these, one died of local recurrence and the other died of multiple metastases. The overall survival for all patients with primary ACC was 72% for 5 years.

DISCUSSION

Primary TBACC is very rare, accounting for only 0.1%–0.2% of all respiratory malignancies, which commonly arises at the distal one third of the trachea. ⁵ , ⁶ TBACC is characterized by a slow progression and a tendency to infiltrate and cross the tracheobronchial cartilage. Due to the non‐specific symptoms and the tumour growing in the lumen or along the wall, diagnosis is often missed. ⁷ Symptoms are vague and are often treated for conditions such as asthma or upper respiratory tract infection for months before being diagnosed. ⁸

The pre‐treatment imaging modality performed commonly in the evaluation of TBACC was CT scan and bronchoscopy. ⁹ CT imaging can determine the tumour location, specify its endoluminal, peritracheal and peri‐bronchial extension, determine regional invasion and lung metastasis, and provide important information for treatment options. ⁹

Bronchoscopy reveals the location and growth of the tumour and allows the performance of biopsies for pathological diagnosis. ¹⁰ Nowadays, an endobronchial echography is helpful to determine the extension through the bronchial wall. ¹¹

MRI and PET‐CT were adopted in relatively little cases, their contribution in the diagnosis of TBACC needs to further evaluate. ⁹

Treatment options include surgery alone, radiation therapy alone, or a combination. Complete surgical resection of the lesion has been considered as the curative treatment. The 5‐year survival rate after surgery is 85%, while that for patients without surgery is only 63.7%. ¹²

Choosing the right way to go is an essential step. Median sternotomy, anterolateral thoracotomy, posterolateral thoracotomy, bilateral thoracotomy, hemi‐clamshell or clamshell can be used to approach lower trachea, carina and tracheobronchial angle, while cervicotomy is used for cervical lesion. ¹³ The type of incision varies according to the site of the tumour, and therefore patient's positioning depends on this choice.

TBACC are usually operated on by direct surgical resection of the trachea and airway reconstruction.

The extent of surgical resection is limited by tracheal length, and it is generally accepted that the resected length cannot exceed 6 cm or 50% of the total length.

Recent studies have suggested that lymph node ratio and positivity are important prognosticators and that their dissection should be considered in TBACC. ⁸

Because of the limited scope of tracheal resection and the tendency to submucosal extension of TBACC, complete resection is not always achievable. In a review of literature including 76 articles and 1252 cases of TBACC, Juntao Ran and al ⁹ noted that positive rate of resection margin were 59%–63%.

When performing a complete resection of TBACC and achieving negative surgical margins are difficult, an adjuvant radiotherapy as a multi‐modal treatment approach is recommended. ¹⁴

Previous studies suggested that the patients underwent radiotherapy after incomplete resections had a better outcome than those without radiotherapy. It is often utilized postoperatively to increase the survival rate and decrease the risk of local recurrence and distant metastases. ⁴ , ¹⁴

Multidisciplinary treatment including radiotherapy and chemotherapy may be needed to obtain lower rates of local recurrence, distant metastases, and better prognosis.

Literature review only found a limited number of patients subject to chemotherapy, and no study has directly addressed this issue. Thus, the efficacy of chemotherapy for TBACC needs further investigation.

For patients who are not suitable for surgery or radiotherapy, treatment methods such as bronchoscopy ablation and stent placement can also be used. ¹⁵ Future studies with a larger sample size and longer follow‐up period should be conducted to identify prognostic factors of TBACC.

In conclusion, TBACC is a rare malignant tumour. Curative treatment is a real challenge. Complex resection is associated with high postoperative morbidity and mortality rates. When complete resection is not achieved, incomplete resection with adjuvant treatments would also provide a promising prognosis.

AUTHOR CONTRIBUTIONS

Kaouther Ben Amara and Imen Bouassida contributed to patient care, literature review and drafting of the manuscript. Mariem Affes contributed to radiologic analysis and editing the manuscript. Rahma Ayadi and Ayda Ayadi‐Kaddour interpreted histopathological specimens and provided pathology images. Amina Abdelkbir, Mahdi Abdennadher, and Salma Ben Othmen contributed to the critical review of the manuscript and supervised the study. Hazem Zribi and Adel Marghli contributed to the critical review of the manuscript. The final manuscript was reviewed and approved by all authors.

CONFLICT OF INTEREST STATEMENT

None declared.

ETHICS STATEMENT

The authors declare that appropriate written informed consent was obtained for the publication of this manuscript and accompanying images.

Ben Amara K, Bouassida I, Ayadi R, Affes M, Abdelkbir A, Abdennadher M, et al. Primary tracheo‐bronchial adenoid cystic carcinoma: A surgical series with literature review. Respirology Case Reports. 2025;13(1):e70062. 10.1002/rcr2.70062

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.