Tracheal Tumors 

Updated: Sep 23, 2019
Author: Brian J Daley, MD, MBA, FACS, FCCP, CNSC; Chief Editor: Mary C Mancini, MD, PhD, MMM 

Overview

Practice Essentials

Tracheal neoplasms occur infrequently, accounting for fewer than 1% of all malignancies.[1, 2, 3]  Figures from the National Cancer Institute (NCI) Surveillance, Epidemiology and End Results (SEER) 1973-2004 database indicated tat primary carcinomas of the trachea occur at a rate of 2.6 new cases per million people per year. During this period, 578 cases were reported: 322 men (55.7%) and 256 women (44.3%).[4]

Patients with tracheal tumors can present with catastrophic airway obstruction. In addition to primary neoplasms of the trachea, secondary tracheal involvement can occur from tumors of surrounding tissues such as thyroid, esophagus, larynx, and lung.

According to the SEER 1973-2004 database, 80% of all primary tumors of the trachea during this period were malignant; squamous cell carcinoma (SCC) was the predominant histology type (44.3%), followed by adenoid cystic carcinoma (ACC; 16.3%).[4] The remaining tumors were widely varied and included both malignant and benign histotypes. 

Tracheal tumors are eminently treatable when diagnosed in the early stages. However, their usually insidious onset often leads to a delay in diagnosis, making these potentially treatable lesions difficult to manage and often fatal. Thus, early diagnosis is the most important factor affecting overall survival.

Surgical resection is the mode of treatment with the best hope for cure. Radiotherapy can be offered if the patient cannot tolerate surgical treatment. Chemotherapy can also be given after initial treatment with surgery, radiotherapy, or both. Laser removal of the intratracheal tumor is usually performed for palliation.

For patient education resources, see the Procedures Center, as well as Bronchoscopy.

Anatomy

The average length of the adult trachea is 11 cm from the inferior border of the cricoid cartilage to the carinal spur. The trachea courses from an immediately subcutaneous position in the neck to a position against the esophagus and prevertebral fascia at the carinal level.

There are 18-22 cartilaginous rings in the human trachea, with approximately two rings per centimeter. The airway in an adult is roughly elliptical. The only complete cartilaginous ring in the normal airway is the cricoid cartilage of the larynx.

Calcification of the cricoid is not unusual, and calcification of other cartilaginous rings occurs with age. The attachments of the trachea allow relatively free vertical movement in relation to other anatomic structures. The most fixed point below the cricoid lies where the aortic arch forms a sling over the left main bronchus.

Pathophysiology

The tracheal mucosa is columnar and ciliated. It is closely apposed to the tracheal cartilages and to the interannular tissues between them. Mucous glands are liberally present. In patients with chronic bronchitis, particularly those who smoke heavily, squamous metaplasia may occur.

Typically, tracheal tumors grow slowly. Benign neoplasms tend to be smooth, rounded masses less than 2 cm in length. The presence of calcium seen on plain radiography films, though common, does not reliably differentiate benign and malignant tumors. Malignant tumors, specifically SCCs, may be exophytic or ulcerative.

Etiology

Benign tumors can arise from any of the tissues present in the trachea. Malignant tumors probably follow a carcinogenesis similar to that of lung cancers. Most of these tumors occur sporadically. Apart from squamous papillomas, which have been associated with viral infection, no consistent etiology has been found. Smoking is a known risk factor.

Epidemiology

Primary tracheal tumors are very rare, occurring at a rate of approximately 0.1 per 100,000 population. Most (80-90%) are malignant.[5] The incidence of primary tracheal carcinoma is much lower than that of laryngeal or endobronchial cancer. Lung cancers are 180 times more common than tracheal malignancies. Smoking is a commonly associated risk factor.[3] In some studies, 40% of patients had prior, concurrent, or later carcinoma of the oropharynx, larynx, or lung.

Tracheal tumors are three times more common in males than in females. Peak incidence occurs in the fifth and sixth decades of life.

Prognosis

Median survival for all patients after diagnosis of malignant tracheal tumors is 6 months, but survival time varies widely, depending on the histologic type of the tumor. General overall 5-year survival for all patients with tracheal carcinoma was 27.1% (95% confidence interval, 23.1-33.3%), with an improved outcome for patients with localized disease versus regional or distant disease. A tumor histology of SCC yielded a 5-year survival rate of 12.6% versus 74.3% for ACC.[4] Following resection, carcinoid tumors carry excellent 5-year and 10-year survival rates in most series (95% and 90%, respectively).

According to Xie et al, radiation therapy may improve outcomes in patients with primary squamous cell tracheal malignancies.[6] Furthermore, there was a statistically significant survival benefit for patients who underwent any type of surgical therapy as compared with those who did not.

 

Presentation

History and Physical Examination

The presentation of primary tumors of the trachea is variable. Usually insidious in onset, tracheal tumors often present with signs and symptoms of upper airway obstruction. In a series of 329 patients with primary tracheal malignancies, dyspnea was the most frequent symptom (71%), followed by cough (40%), hemoptysis (34%), asthma (19.5%), and stridor (17.5%).[3] These symptoms are often misinterpreted, leading to a delay in diagnosis and a trial of corticosteroids before the correct diagnosis is made. Symptoms related to involvement of adjacent structures, such as hoarseness and dysphagia, are less common (7%).

The first symptom may be shortness of breath after activity, which gradually worsens. Acute respiratory difficulty may not be present until the airway is almost completely occluded, which explains why it may be rapidly fatal. A persistent cough, wheezing, or stridor may be noted, as may recurrent attacks of respiratory obstruction caused by secretions.

Delay in diagnosis occurs because the pulmonary fields remain normal on a chest radiograph.[3] If the patient has hemoptysis, a diagnosis is more likely to be made because bronchoscopy will be performed even in the presence of a normal chest radiograph. This is more common in patients with squamous cell tumors.

Patients may also present with repeated episodes of either unilateral or bilateral pneumonia that respond to antibiotics and physiotherapy. In the absence of hemoptysis, a diagnosis of adult-onset asthma is often made, thus delaying definitive treatment. In one series, delayed diagnosis of more than 6 months after symptoms onset occurred in one third of patients.

Squamous cell carcinoma (SCC) is the most rapid in onset, often leading to hemoptysis or obstructive symptoms as presenting features. It is more prone to be exophytic and ulcerative in nature and is most common in male smokers. SCC metastasizes to regional lymph nodes and can invade the mediastinum in more aggressive forms or in late stages. Distant metastases are common, most often to bone.

Adenoid cystic carcinoma (ACC), or “cylindroma,” occurs almost as frequently as SCC; together, the two types account for two thirds of primary tracheal malignancies. ACC is slower in onset than SCC, often having a prolonged course of clinical symptoms. ACC may extend over long distances in the submucosa. It too spreads to regional lymph nodes, though less often than SCC does. ACC often displaces mediastinal structures in late stages before actually invading them. Metastases to the lung are not uncommon. The male-to-female ratio is almost equal, and ACC is less commonly associated with smoking.

One quarter of tracheal tumors are neither ACC nor SCC. This heterogeneous group of tumors has varying degrees of malignancy and include both epithelial and mesenchymal histotypes. In a review over 40 years, Gaissert et al assessed 360 tumors and documented 90 unusual tumors.[7] Unusual tumor types included the following:

  • Carcinoid (11)
  • Mucoepidermoid (13)
  • Nonsquamous bronchogenic carcinoma (15)
  • Lymphoma (2)
  • Melanoma (1)

Thirty-four lesions were benign.

 

Workup

Approach Considerations

Tracheal lesions may be evaluated by means of bronchoscopy or radiographic imaging (see below).

Besides allowing biopsy for tissue diagnosis, newer modalities such as lasers can be applied endoscopically.

Imaging Studies

The initial study invariably is a plain chest radiograph, which usually shows normal lung fields.[3] This result can delay the diagnosis of a tracheal tumor. Standard chest radiography is insensitive in the detection of tracheal neoplasms, and fewer than 50% of tracheal tumors are diagnosed by using this modality.[3] Diagnostic clues to the presence of a tracheal tumor on chest radiographs include the following:

  • Tracheal narrowing
  • Postobstructive atelectasis or pneumonia
  • Abnormal calcification

Planar tomography is much more sensitive in displaying tracheal tumors, but computed tomography (CT) is currently the imaging technique of choice.[3] Planar tomography was used before CT became the standard technique, primarily for better localization of lesions.

Conventional CT protocols may miss small lesions. CT is best performed by using a spiral (helical) scanner, which allows precise volumetric acquisition and multiplanar image display. Spiral CT can also help differentiate mucosal from submucosal masses and reveal the extent of submucosal spread.[3]

Magnetic resonance imaging (MRI) may be applied to tracheal tumors for better evaluation of extension into tissue planes and vascular anatomy.

Bronchoscopy

Bronchoscopy is part of the evaluation for most pneumonic processes. Its role is to help identify obstructions, whether intrinsic to the tracheal/bronchial lumen or extrinsic and causing compression. Bronchoscopy should be performed under optimal conditions because the risk of acute airway compromise is high.

Bronchoscopy remains the criterion standard because it provides definitive evaluation of the airway, allows assessment of gives anatomic considerations, and is capable of obtaining tissue samples for diagnosis.

Histologic Findings

Malignant tumors

Malignant bronchial gland tumors arise from salivary glands with the trachea.

Adenoid cystic carcinoma (ACC) is seen primarily in individuals aged 13-79 years and is evenly distributed between males and females. It grows so slowly in many patients that it appears to be benign in behavior, even after metastases have occurred to the lungs. Some lesions are highly malignant and spread to pleura and lungs before they are discovered. Remote metastasis occurs most often to lung and bone. This cell type constitutes 90% of tumors. Mucoepidermoid carcinoma, mucinous cystadenoma, and pleomorphic adenoma have all been reported in decreasing frequency.

Bronchial carcinoids are derived from the neuroendocrine cell line, as are other amine precursor uptake and decarboxylation cell tumors. They are part of a spectrum of tumors derived from the same cell line, which ranges from typical carcinoids (which usually follow a benign course) to the more aggressive atypical carcinoids and the highly malignant small cell lung cancer (SCLC). The cells are capable of secreting active peptide hormones, as do other carcinoids. This is rarely of clinical significance, because the carcinoid syndrome is quite rare with bronchial or tracheal tumors. Thus, most tumors present with obstructive-type symptoms.

In a newer classification, carcinoid tumors are part of a larger group of lesions referred to as neuroendocrine tumors of the lung. These neuroendocrine tumors include histologically low-grade tumors; typical and atypical carcinoids; and histologically high-grade lesions, large cell neuroendocrine carcinoma, paraganglionoma, and small cell carcinoma. In addition, squamous cell carcinoma (SCC), adenocarcinoma, and large cell carcinoma may exhibit neuroendocrine features. This classification is likely applicable to lesions occurring in the trachea and the lung.

SCC may present as a well-localized lesion of exophytic type or as an ulcerating lesion. Multiple lesions with interspersed normal trachea and superficial infiltrating carcinoma, which may extend over the whole length of the trachea, also occur. Approximately one third of the patients have mediastinal or pulmonary metastases at the time of initial diagnosis. The distribution of SCC of the trachea is comparable to that of squamous bronchogenic carcinoma with respect to age (50-70 years) and sex (male-to-female ratio, 3:1).

Metastatic tumors have also been reported.

Benign tumors

Squamous papillomas are the most common of the benign tumors and are associated with human papillomavirus types 6 and 11. They frequently occur in the larynx and present as vocal changes. They appear as irregular, papillary, or villous processes covered by thick squamous epithelium blending into the normal respiratory epithelium. They may represent a premalignant type of lesion. Simple extirpation results in almost universal recurrence, and radical resection is advocated for complete removal. Modern technological modalities for control are being applied to avoid radical resection.

Cartilaginous tumors are next in frequency. They appear as gray-to-white firm masses with focal gritty areas secondary to calcification and are composed of cartilage and bone cells with an intact overlying mucosa. Cartilaginous tumors generally occur in the fifth and sixth decades of life and carry a potential for sarcomatous change. Complete resection is indicated.

Other tumors

Other tracheal tumors occur but are exceedingly rare. These include the following:

Thyroid tissue may be present ectopically within the trachea. This ectopic tissue also has a potential for malignant change and should be excised.

Staging

No standard staging classification for primary tracheal tumors has been widely accepted in the literature. Historically, all tracheal tumors were defined as stage IV lung cancer on the basis of American Joint Committee on Cancer (AJCC) staging criteria, which derived from the tumor-node-metastasis (TNM) classification. In 2004, however, Bhattacharyya delineated a staging system for primary tracheal tumors that showed a distinct survival advantage in stage I and stage II disease.[8] This system is as follows:

  • TX: Unknown or unable to be assessed
  • T1: Primary tumor confined to trachea, < 2 cm
  • T2: Primary tumor confined to trachea, >2 cm
  • T3: Spread outside the trachea but not to adjacent organs or structures
  • T4: Spread to adjacent organs or structures
  • N0: No evidence of regional nodal disease
  • N1: Positive regional nodal disease
  • NX: Unknown or unable to be assessed

In terms of the TNM classification, stage I disease is defined as T1N0, stage II is T2N0, stage III is T2N0, and stage IV is T4N0 or TanyN1 or any distant metastasis. Stage for stage, ACC has the better prognosis, with reported 5-year survival rates of 66-100% and 10-year survival rates of 51-62%. SCC has a reported 5-year survival rate of 10% and a 10-year survival rate of 35-40%. Bhattacharyya's paper demonstrated a clear survival advantage for stage I and stage II disease, citing 5-year survival rates of 70-80%.[8] T4 disease or any nodal involvement confers a dismal prognosis, with 5-year survival rates of 15% or less.

 

Treatment

Approach Considerations

Surgery is usually indicated once diagnosis of a primary tracheal neoplasm is made. This is because these patients tend to progress rapidly once symptomatic because of the near-total tracheal luminal obstruction that is frequently present. Tracheal tumors are likely to be found during evaluation for more common pulmonary conditions (eg, pneumonia, cancer, and adult-onset asthma).

Because of the imminent threat to an adequate airway, urgent surgical intervention for primary tracheal tumors is not usually contraindicated, especially when patients are symptomatic. Bronchoscopic biopsy is contraindicated in the presence of highly vascular tumors (eg, hemangiomas).

Radiotherapy can be offered if the patient cannot tolerate surgical treatment. Chemotherapy can also be given after initial treatment with surgery, radiotherapy, or both. Laser removal of the intratracheal tumor is usually performed for palliation.

As newer modalities such as laser ablation and cryoablation undergo further development, treatment options may change. Furthermore, there is much promise for newer procedures in the field of tracheal reconstruction that could improve the quality of life for those affected by tracheal malignancy and other tracheal disorders. Treatment options that are being investigated include the following:

  • Composite autografts
  • Allografts
  • Chimeric autografts and allografts
  • Tissue-engineered grafts
  • Prosthetic scaffolds
  • Use of free-tissue vascularized carriers
  • Tracheal allotransplantation

Many of these techniques require further research for validation.[9, 10]

Medical Therapy

In general, medical therapy has not been useful in the treatment of tracheal tumors. Successful treatment of squamous papillomatosis with interferon has been reported. Steroids once were used in tracheal hemangiomas, most of which now are treated by observation only because spontaneous regression is common.

Some case studies have reported that combination chemotherapy with concurrent carboplatin and paclitaxel, or concurrent nedaplatin and 5-fluorouracil together with radiation therapy, might be an effective treatment option for unresectable adenoid cystic carcinoma (ACC).[11, 12]

Reports of high-dose brachytherapy to treat primary tracheal tumors can be found in the literature[13] ; however, these cases generally involved tumors that either were recurrences or were unresectable because of the patient's condition. In isolated cases, local control was achieved with brachytherapy alone.

In a study of patients with tracheal tumors who received palliative treatment with endotracheal brachytherapy alone, Nguyen et al found that this approach yielded effective palliation and symptomatic improvement while giving rise to minimal toxicity.[14]  In a small series, Doggett et al reported good short-term results with the use of percutaneous computed tomography (CT)-fluoroscopy-guided radioisotope seed placement to manage ACC of the trachea.[15]

There is some evidence to suggest that immunotherapy (eg, nivolumab) may eventually prove useful in the treatment of patients for whom conventional therapies have failed.[16]

Surgical Therapy

Surgical resection is the mode of treatment with the best hope for cure. In the series of 198 patients reported by Grillo and Mathisen, 70 (35%) had squamous cell carcinoma (SCC).[17] Of these, 44 (63%) were resected, with an operative mortality of 5%. The overall survival rate was 27% at 3 years and 13% at 5 years.

Laser resection as definitive treatment is appropriate for the following patients:

  • Patients with metastatic disease
  • Patients unable to tolerate primary resection
  • Patients with tumors that are too locally invasive to allow excision

In such patients, a laser procedure with stent placement may improve airway patency and allow for other definitive treatments.

The rapid expansion of technology has given rise to less invasive therapeutic options (eg, stenting, allografts).[18] Tracheobronchial stenting offers a minimally invasive palliative therapy for patients with unresectable malignant central airway obstruction that appears to be mostly beneficial in the short term.[19] This procedure provides symptomatic relief but seems to be less beneficial after 30 days as a result of tumor and tissue ingrowth. Indications for stenting include the following:

  • Endoluminal tumor
  • Malignant stricture
  • Extrinsic compression, except for extrinsic compression that is secondary to vascular compression, because this places patients at too high a risk for stent erosion and hemorrhage

In 2011, Seifalian et al, from the University College of London, produced the first completely synthetic trachea. Made of nanocomposite material, the synthetic trachea was transplanted into a patient whose own windpipe was damaged by cancer.[20] The operation was performed in Sweden at the Karolinska University Hospital in conjunction with the Karolinska Institute.

The synthetic windpipe’s wide and porous surface area allowed the stem cells taken from the patient's bone marrow and lining cells from the nose to be seeded with the patient's tissue. Within days, a synthetic windpipe, which essentially was the patient’s own, was created in a revolving bioreactor and then transplanted into the patient. This technique allows the patient to provide the stem cells to create the new trachea, avoiding a long waiting period to find a donor and eliminating the need for the antisuppressant drugs that other transplant patients must take.

Operative approach

Because of potential airway compromise, surgical intervention generally proceeds rapidly from the time of diagnosis.

Surgical treatment of proximal airway tumors presents some technical challenges specifically related to the maintenance of acceptable ventilation beyond the area of obstruction. Techniques have been developed for distal intubation during the resection of the tumor. Percutaneous transtracheal ventilation has been successfully used for laser endoscopic treatment of subglottic tumors. A study by Ding et al found that therapeutic bronchoscopy could significantly alleviate central airway obstruction, reduce shortness of breath, and improve quality of life for patients with tracheal neoplasms.[21]

Tumors of the upper third of the trachea can be approached transcervically via a standard collar incision. Tumors in the middle third of the trachea may require a partial or complete median sternotomy in addition to a cervical incision. Distal-third tumors are resected easily via a right thoracotomy to avoid the aortic arch.

Intraoperative bronchoscopy is used for accurate tumor localization. Lesions are resected with attempts to preserve as much trachea and lung tissue as possible. However, lobectomy may be necessary to ensure negative margins and node assessment. Using sleeve resections of the tracheal or bronchial tissue can preserve lung tissue.

Conventional wisdom has been that, at most, only 2 cm could be removed in order for the trachea to be dependably reconstructed in an end-to-end manner. Longer lesions are managed by means of lateral resection, with as wide a bridge of tracheal tissue as possible left to maintain the rigidity and patency of the airway.

Because the defects are usually too large to be closed by suturing, various materials are used as patches. Prosthetic materials usually fail because the bed of mesenchymal tissue in which the foreign body lies becomes, in effect, a chronic ulcer and responds characteristically because it is adjacent to a contaminated epithelial surface. Granulation tissue then proliferates in an attempt to heal the area, producing obstruction or stricture. Migration of the prosthesis may lead to erosion of major vessels.

Complex reconstructions that use the patient's own tissues generally have been successful only in the neck, where delayed healing can be accepted and multistaged procedures are possible. Reconstruction in the mediastinum requires that a fully-fashioned rigid tube with an epithelial lining be present at the conclusion of the initial operation.

Prosthetics such as nitinol mesh stents with overlapping cervical myocutaneous flaps to protect the neotrachea have been described.[22] The pectoralis major and latissimus dorsi myocutaneous flaps have also been successfully used in complex anterior mediastinal tracheostomy reconstruction techniques.[23]

Studies indicate that as much as half of the trachea can be removed and primary anastomosis achieved if extensive mobilization techniques are used. These techniques include the following:

  • Division of the inferior pulmonary ligament
  • Mobilization of the right mainstem bronchus from the pulmonary artery and vein and from the pericardium
  • Release of the larynx by separation of its thyrohyoid attachments

Grillo recommended using absorbable polyglactin for all tracheal anastomoses to minimize granuloma formation.[24] Usually, greater lengths of trachea may be removed in younger patients because of the greater elasticity of the trachea.

Complications

Less-than-complete tracheal resection may lead to local recurrence. This may be acceptable if morbidity risks limit operative choice. In a retrospective study by Chen et al that involved 52 patients with primary ACC of the trachea, the investigators suggested that postoperative radiotherapy should be recommended for patients with incomplete resections.[25]

Experience is growing with the use of stents to temporize before definitive resection or to treat patients who are not surgical candidates.[26, 27] Complications from bronchial or tracheal stenting include the following:

  • Rupture
  • Granulation tissue
  • Residual scarring
  • Stenosis and bleeding

If diagnosis is delayed, tracheoesophageal fistula and tracheoinnominate fistula can occur.

Complications of tracheal surgery include the following:

  • Restenosis
  • Anastomotic and sternal dehiscence
  • Anterior spinal cord ischemia
  • Acquired respiratory distress syndrome
  • Fistula formation

Reported rates are low and increases with increasingly higher levels of resection.[28, 29] In one series of primary resection and anastomosis, the ability to definitively remove the airway after surgery approached 100%.[30]

Long-Term Monitoring

For patients with benign lesions, serial follow-up examination is recommended, especially if tracheal resection is not performed.

For those with malignant lesions, follow-up examination similar to that for lung cancer is appropriate, with serial computed tomography (CT) scans over the following 5 years. Preoperative radiation therapy is administered given for ACC and adjuvant radiation for mucoepidermoid carcinoma. Combined-modality therapy may be considered for carcinoid or other neuroendocrine tumors exhibiting more aggressive characteristics than the typical carcinoid lesions. Because of the infrequency of these tumors, most data are retrospective, and series of outcomes are small.