From Medscape – Brian James Daley, MD, MBA, FACS, FCCP, CNSC et al.
Tracheal neoplasms occur infrequently, accounting for less than 1% of all malignancies.[1, 2] In the nearly 3 decades between 1962 and 1989, 198 patients with primary neoplasms of the trachea were treated at Massachusetts General Hospital. The incidence of primary tracheal tumors has been estimated to be 2.7 new cases per million per year.
Of all primary tumors of the trachea, 80% are malignant; adenoid cystic carcinoma and squamous cell carcinoma are the most common, comprising two thirds of all tracheal tumors. The remainder is widely varied and includes both malignant and benign histotypes. Despite their rarity, their usually insidious onset often leads to a delay in diagnosis, making these potentially treatable lesions difficult to treat and often fatal.
History of the Procedure
Tracheostomy is one of the oldest procedures in surgery, first appearing in surgical literature in 1649 and becoming a common surgical procedure by 1718 by the German physician Lorenz Heister. The first postmortem description of a tracheal fibroma was by Lieutaud in 1767. In 1861, Turck used indirect laryngoscopy to diagnose a tracheal tumor in a living patient. Direct endoscopic visualization of a tracheal neoplasm was reported by Killian in 1897.
Patients with tracheal tumors can present with catastrophic airway obstruction. Tracheal tumors are eminently treatable when diagnosed in the early stages.
Primary tracheal tumors are very rare, occurring in approximately 0.1 person per 100,000 population. Most (80-90%) are malignant. The incidence of primary tracheal carcinoma is much lower than laryngeal or endobronchial cancer. Lung cancers are 180 times more common than tracheal malignancies. Smoking is a commonly associated risk factor. Forty percent of patients in some studies had prior, concurrent, or later carcinoma of oropharynx, larynx, or lung. Tracheal tumors are 3 times more common in males than in females. Peak incidence occurs in the fifth and sixth decades of life.
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.
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 in those who smoke heavily, squamous metaplasia may occur.
Typically, tracheal tumors grow slowly. Benign neoplasms tend to be smooth, rounded masses shorter 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 squamous cell carcinomas, may be exophytic or ulcerative.
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%).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 might be seen, as might recurrent attacks of respiratory obstruction caused by secretions.
Delay in diagnosis occurs because the pulmonary fields remain normal on a chest radiograph. 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 patient
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. It 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, collectively comprising two thirds of primary tracheal malignancy. It 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, although less often than SCC. ACC often displaces mediastinal structures in late stages before actually invading them. Metastases to the lung are not uncommon. The male to female ration 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 reviewed 360 tumors, reviewing 90 unusual tumors.Unusual tumor types included carcinoid (11), mucoepidermoid (13), nonsquamous bronchogenic carcinoma (15), lymphoma (2), and melanoma (1). Thirty-four lesions were benign.
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.
See Intraoperative Details.
The average length of the adult trachea is 11 cm from the inferior border of the cricoid cartilage to the carinal spur. It 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 2 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.
Because of imminent threat to 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).
Laboratory examination is not particularly helpful or revealing in the diagnosis or treatment of tracheal tumors.
Tracheal lesions may be evaluated using bronchoscopy or radiographic imaging, as follows:
The initial study invariably is a plain chest radiograph, which usually shows normal lung fields. This can delay diagnosis.
Standard chest radiographs are insensitive in the detection of tracheal neoplasms, and less than half of tracheal tumors are diagnosed using this modality. Diagnostic clues to the presence of a tracheal tumor on chest radiographs include (1) tracheal narrowing, (2) postobstructive atelectasis or pneumonia, or (3) abnormal calcification.
Planar tomography is much more sensitive in displaying tracheal tumors, but CT scan is currently the imaging technique of choice.Planar tomography was used before CT scans became the standard technique, primarily to better localize lesions.
Conventional CT scan protocols might miss small lesions. CT scan is best performed using a spiral or helical scanner, which allows precise volumetric acquisition and multiplanar image display. Spiral CT scan might also help differentiate mucosal from submucosal masses and reveal the extent of submucosal spread.
MRI is now being applied to tracheal tumors to better evaluate extension into tissue planes and vascular anatomy.
Bronchoscopy remains the criterion standard because it provides definitive assessment of the airway, gives anatomical considerations, and can obtain a tissue diagnosis.
Bronchoscopy is part of the evaluation for most pneumonic processes. Its role is to help identify obstructions, either 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.
Besides allowing biopsy for tissue diagnosis, newer modalities such as lasers can be applied endoscopically.
Malignant bronchial gland tumors arise from salivary glands with the trachea.
Adenoid cystic carcinoma: This tumor 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: These tumors 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. The cells are capable of secreting active peptide hormones, as do other carcinoids. Rarely is this of clinical significance because the carcinoid syndrome is quite rare with bronchial or tracheal tumors. Thus, most tumors present with obstructive-type symptoms.
Neuroendocrine tumors: In a newer classification, carcinoid tumors are part of a larger group of lesions referred to as neuroendocrine tumors of the lung. These include histologically low-grade tumors; typical and atypical carcinoids; and histologically high-grade lesions, large cell neuroendocrine carcinoma, and small cell carcinoma. In addition, squamous cell carcinomas, adenocarcinomas, and large cell carcinomas may exhibit neuroendocrine features. This classification is likely applicable to lesions occurring in the trachea and the lung.
Squamous cell carcinoma: This 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. Squamous cell carcinoma of the trachea is distributed comparably to squamous bronchogenic carcinoma with respect to age (50-70 y) and sex (male-to-female ratio of 3:1).
Metastatic tumors have also been reported.
Squamous papillomas: These 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: 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. Generally occurring in the fifth and sixth decades of life and with a potential for sarcomatous change, complete resection is needed.
Other tracheal tumors are exceedingly rare and include hamartomas, hemangiomas, neurilemomas, leiomyomas, oncocytomas, schwannomas, and histiocytomas. Thyroid tissue may be present ectopically within the trachea. This too has a potential for malignant change and should be excised.
No standard staging classification for primary tracheal tumors has been widely accepted in the literature. Previously, all tracheal tumors have been defined as Stage IV lung cancer by current staging criteria from the American Joint Committee on Cancer (AJCC). However, a recent publication by Bhattacharyya in Otolaryngology–Head and Neck Surgery delineates a staging system for primary tracheal tumors that shows distinct survival advantage in Stage I and Stage II disease. Although this system has not yet been adopted by the AJCC, it is outlined below.
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
By the previously outlined TNM classification, Stage I disease is defined as T1N0, Stage II is T2N0, Stage III is T2N0, and Stage IV is T4N0 or any TN1 or any distant metastasis. Stage for stage, adenoid cystic carcinoma has the better prognosis, with 5-y survival rates cited to be 66-100% and 10-y survival rates of 51-62%. Squamous cell carcinoma has a cited 5-y survival rate of 10% and a 10-y survival rate of 35-40%. This paper demonstrates a clear survival advantage for Stage I and Stage II disease, giving 70-80% 5-y survival rates. T4 disease or any nodal involvement confers a dismal prognosis, with 5-y survival rates of 15% or less.
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 reports of high dose brachytherapy to treat primary tracheal tumors can be found in the literature; however, these cases were either recurrences or were unresectable because of patient condition. In isolated cases, local control was achieved with brachytherapy alone.
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.
In the series of 198 patients reported by Grillo and Mathisen, 70 (35%) had squamous cell carcinoma. Of these, 44 (63%) were resected, with an operative mortality rate of 5%. The overall survival rate was 27% at 3 years and 13% at 5 years.
Laser resection as definitive treatment is appropriate for (1) patients with metastatic disease, (2) patients unable to tolerate primary resection, or (3) 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.
Novel therapies are reported as the relative infrequency of these tumors and the rapid expansion of technology offers less invasive therapeutic options (eg, stenting, allografts). Lemaire et al conclude that tracheobronchial stenting offers a minimally invasive palliative therapy for patients with unresectable malignant central airway obstruction that is mostly beneficial in the short-term. 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 endoluminal tumor, malignant stricture, tracheoesophageal fistula, and extrinsic compression, except for extrinsic compression that is secondary to vascular compression because it places patients at too high a risk for stent erosion and hemorrhage.
In 2011, Professor Alex Seifalian et al of 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. 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 bio-reactor 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 anti-suppressant drugs that other transplant patients must take.
Because of potential airway compromise, surgical intervention generally proceeds rapidly from time of diagnosis.
The 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 the laser endoscopic treatment of subglottic tumors.
Tumors of the upper third of the trachea can be approached transcervically by 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 through 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 reconstructed end-to-end dependably. Longer lesions are managed by lateral resection, leaving as wide a bridge of tracheal tissue as possible to maintain rigidity and patency of the airway.
Because the defects are usually too large to be closed by suture, 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 recently described by Cai et al. Thepectoralis major and latissimus dorsi myocutaneous flaps have also been successfully used in complex anterior mediastinal tracheostomy reconstruction techniques.
Studies indicate that as much as half of the trachea can be removed and primary anastomosis achieved if extensive mobilization techniques are used. These include (1) division of the inferior pulmonary ligament, (2) mobilization of the right mainstem bronchus from the pulmonary artery and vein and from the pericardium, and (3) release of the larynx by separation of its thyrohyoid attachments. Grillo has recommended using absorbable polyglactin (Vicryl) for all tracheal anastomoses to minimize granuloma formation. Usually, greater lengths of trachea may be removed in younger patients because of the greater elasticity of the trachea.
Benign lesions: Serial follow-up examination is recommended, especially if tracheal resection is not performed.
Malignant lesions: Follow-up examination similar to that for lung cancer is appropriate, with serial imaging using CT scan over the next 5 years. Preoperative radiation is given for adenoid cystic carcinoma and adjuvant radiation for mucoepidermoid carcinoma. Consideration may be given to combined-modality therapy in carcinoid or other neuroendocrine tumors exhibiting more aggressive characteristics than the typical carcinoid lesions. Because of the infrequent nature of these tumors, most data are retrospective and series of outcomes are small.
Less-than-complete tracheal resection may lead to local recurrence. This may be acceptable if morbidity risks limit operative choice. Experience is growing with stents to temporize before definitive resection or to treat patients who are not surgical candidates.[13, 14] Complications from bronchial or tracheal stenting include rupture, granulation tissue, residual scarring, and stenosis and bleeding.
If diagnosis is delayed, tracheoesophageal fistula and tracheoinnominate fistula can occur.
Complications of tracheal surgery include restenosis, anastamotic and sternal dehiscence, anterior spinal cord ischemia, acquired respiratory distress syndrome, and fistula formation. Reported rates are low and increases with increasingly higher levels of resection.[15, 16] The ability to definitively remove the airway after surgery approaches 100% in one series of primary resection and anastomosis.
Outcome and Prognosis
Median survival for all patients after diagnosis of malignant tracheal tumors is 6 months, but survival time varies widely with different histological types of tumor. Patients who have adenoid cystic carcinoma or mucoepidermoid carcinoma have significantly better survival than those with other histologic types. Squamous cell carcinoma carries the worst prognosis (mean survival 44 months, 5-y survival 34%). Adenoid cystic carcinoma exhibited a mean survival of 115 months with a 78% 5-y survival. Following resection, carcinoid tumors carry excellent 5-y and 10-y survival rates in most series (95% and 90%, respectively).
Future and Controversies
As newer modalities such as laser and cryoablation are developed, treatment options may change.