Pulmonary Medicine

Tracheal Tumors

What every physician needs to know:

Benign and low- and high-grade malignant tumors arise either from the epithelium or the wall of the trachea. Lesions that are part of the subglottic larynx are included in this discussion because their histology and treatment are similar. Carinal tumors are also considered when their bulk occupies the trachea rather than a unilateral lung or main bronchus. Most tumors that obstruct the tracheal lumen are metastatic and are not of tracheal origin. Primary tracheal tumors are less common than metastatic lesions: primary laryngeal and pulmonary malignancies, particularly those related to smoking, occur far more frequently. For both types, paratracheal lymph nodes are a common site of metastasis.

Therefore, neoplastic obstruction may arise commonly from an extrinsic tumor growing into the trachea and occluding its lumen. Lymph node metastasis is typically high-grade and grows rapidly, so airway obstruction usually occurs in less than three months. Treatment is palliative. Uncommonly, neoplastic obstruction may arise from primary tumors. Depending on the histologic tumor type, average duration of symptoms may vary from a few months in bronchogenic carcinoma to two years or more in adenoid cystic carcinoma. The treatment may be curative.

There are additional challenges associated with primary tumors of the trachea include diagnostic delay, disbelief in the resectability of these tumors, and resectability. Diagnostic delay often occurs because the symptoms of slow-growing tumors like adenoid cystic carcinoma are similar to those of chronic asthma, but they occur in previously healthy individuals and are mistakenly diagnosed as adult-onset asthma. Diagnostic clues are subtle, and they may include audible breathing, inspiratory rather than expiratory obstruction, and lack of response to bronchodilators and steroids.

Disbelief among physicians and surgeons that primary tracheal tumors are resectable results in a low resection rate. Scandinavian epidemiologic studies found a low resection rate, and a multidisciplinary audit of Dutch epidemiologic data suggested that only half of all resectable tumors were actually resected.

Finally, the determination of resectability presents a challenge. Particularly in malignant tumors that involve longer tracheal segments, the maximal resectable length depends on the patient's age and build and the surgeon’s ability to mobilize the tracheal ends under acceptable tension, an assessment that relies on judgment and precludes the use of simple rules.

Classification:

The largest group of primary tracheal neoplasms consists of two common carcinomas: squamous and adenoid cystic carcinoma. Squamous carcinomas, which are more common, display rapid growth, while the less common adenoid cystic carcinomas grow slowly. Because of this growth differential and despite the greater incidence of squamous carcinoma, the number of resectable cases may be similar in individual centers.

Bronchogenic carcinomas other than those of squamous histology are uncommon. A comparison of clinical series with epidemiologic studies exposes important differences in the histologic pattern that are probably explained by inaccurate assignment of tumors in the trachea as “tumors of the trachea” without radiographic or histologic verification.

Among the “uncommon” tracheal tumors are groups of carcinoid tumors, mucoepidermoid carcinomas, sarcomas, and other bronchogenic carcinomas. The vast majority of primary tumors are malignant, and benign tumors occur as “groups of one.” The list of 360 tumors shown in Table 1 comprises the experience at Massachusetts General Hospital over forty years.

Table 1.

Malignant and benign tracheal tumors evaluated in a single center
Malignant tumors Number of patients
Adenoid cystic carcinoma 135
Squamous cell carcinoma 135
Carcinoids 11
Typical 10
Atypical 1
Lymphoma 2
Melanoma 1
Mucoepidermoidcarcinoma 14
Non-squamous carcinoma 15
Small cell carcinoma 5
Adenocarcinoma 4
Large cell carcinoma 4
Adenosquamous carcinoma 2
Sarcoma
Spindle cell sarcoma 6
Chondrosarcoma 3
Leiomyosarcoma 1
Carcinosarcoma (pseudosarcoma) 1
Invasive fibrous tumor 1
Malignant fibrous histiocytoma 1
All malignant 326
Benign tumors
Capillary hemangioma 1
Chondroblastoma 1
Chondroma 2
Fibrous histiocytoma 1
Glomus tumor 1
Granular cell tumor 2
Hamartoma 2
Hemangiomatousmalformation of mediastinum 1
Inflammatorypseudotumor (plasma cell granuloma) 1
Leiomyoma 3
Neurogenic tumor 4
Schwannoma 1
Plexiform neurofibroma 1
Peripheral nerve sheath tumor 1
Atypical schwannoma 1
Paraganglioma 1
Pleomorphic adenoma 3
Pyogenic granuloma 1
Squamous papillomas 9
Multiple 5
Solitary 4
Vascular tumor of borderline malignancy 1
All benign 34
Total 360

Are you sure your patient has a tracheal tumor? What should you expect to find?

Considering a tracheal tumor in the differential diagnosis is the most important step in making the diagnosis. However, you would have to consider this diagnosis and be disappointed many times before being rewarded, as these tumors are rare.

The typical symptoms--dyspnea, cough and wheezing--relate to airway obstruction. The rate of progression is determined by tumor-doubling time and individual growth characteristics. Table 2 compares the comorbidities, prior cancers, and symptoms in squamous cell carcinoma--a malignancy caused by smoking or exposure to industrial fumes--to adenoid cystic carcinoma, a tumor without known risk factor. Hemoptysis is often seen in high-grade bronchogenic carcinoma, whereas wheezing is observed in adenoid cystic carcinoma. Tracheal squamous cell carcinoma may arise after prior resection of lung cancer.

Table 2.

Epidemiologic comparison of adenoid cystic and squamous cell carcinoma
ACC SCC χ 2 p Value
Sex (%)
Female 53 32 0.004
Male 46 68
Mean age(median), years 49 (47) 61 (62)
Comorbidities(%)
Smoker 45 89 <0.001
Hypertension 17 29 0.02
EtOH use 5 18 <0.001
Past MI 2 13 0.001
Diabetes mellitus 2 12 0.002
Steroid use 7 7 0.812
Angina 3 6 0.238
Arrhythmia 3 5 0.356
Prior stroke 2 3 0.702
Prior cancers (%)
Lung 1 15 <0.001
Larynx 0 7 0.001
Head and neck 0 4 0.024
Colon 1 1 0.562
Prostrate 1 1 0.562
Oropharynx 0 1 0.156
Other 0 7 0.001
Symptoms(%)
Dyspnea 65 50 0.014
Cough 55 52 0.626
Hemoptysis 29 60 <0.001
Wheeze 44 27 0.003
Stridor 21 27 0.2
Hoarseness 10 13 0.495
Dysphagia 7 7 0.812
Fever 7 4 0.184
Other 12 14 0.495

Audible breathing, even with open-mouth breathing, is characteristic of tumors large enough to cause airway obstruction. Stridor may be either inspiratory or expiratory. Hoarseness does not reliably predict vocal cord involvement or recurrent laryngeal nerve involvement. Nerve function may gradually diminish without leading to hoarseness, while some subglottic tumors may be associated with hoarseness but not vocal cord dysfunction.

Once a tracheal tumor is apparent in radiographic studies, the duration of symptoms allows the physician to consider the likely histologic type. Figure 1 provides guidance regarding the expected tumor type; individual lesions may vary in duration.

Figure 1.

Beware: there are other diseases that can mimic tracheal tumors.

Most other causes of airway obstruction--post-intubation injury, tuberculous airway strictures (though not necessarily in North America), inflammatory stenoses related to collagen vascular disease, idiopathic laryngotracheal strictures, malignant tracheal obstruction by metastatic lymph nodes, and benign or malignant strictures of adjacent structures, larynx, or main bronchi--are more common than primary tracheal tumors are.

A history of endotracheal intubation may indicate a related injury, and some benign lesions may mimic tumors and vice versa. If doubt remains regarding the diagnosis, endoscopy should be performed for biopsy.

How and/or why did the patient develop a tracheal tumor?

The single most common tumor of the trachea is squamous carcinoma. As in tumors in other locations of the upper and lower respiratory tract, this tumor is caused by smoking and other carcinogenic fumes. However, in contrast to carcinoma of the larynx and lung, the incidence is very low, probably because of the more laminar flow inside the trachea that allows less deposition of carcinogen. There are no known other risk factors.

If one were to make a prognosis based on epidemiologic reviews, a “nihilistic” attitude (so termed by Licht and associates) would result since the long-term survival is dismal and surgical resection, radiation, or any other treatment appears to extend survival. The problem with epidemiologic studies is their lack of radiographic and histologic review, which is of critical importance because metastatic malignant airway obstruction is often misdiagnosed as primary tracheal tumor. Where epidemiologic surveys take these factors into account, two observations emerge: some tracheal tumors are not primary to the trachea, and surgical resection is underutilized.

The often quoted annual incidence of one primary tracheal tumor per one million inhabitants should be regarded as a rough estimate and as possibly overestimating the true incidence.

Which individuals are at greatest risk of developing a tracheal tumor?

Patients with a history of lung cancer are at greater risk of developing a second lung cancer in the trachea than are those with no such history, but tracheal tumors are so rare that special surveillance beyond oncologic follow-up cannot be recommended.

What laboratory studies should you order to help make the diagnosis, and how should you interpret the results?

There are no blood tests that predict or confirm the presence of a primary tumor with any reliability. Hemoptysis, unless it is massive, rarely leads to a perceptible decline in hemoglobin, so anemia requires careful evaluation, and metastatic disease should be ruled out. Human papilloma virus (HPV) has not been demonstrated in association with tracheal tumors.

What imaging studies will be helpful in making or excluding the diagnosis of tracheal tumor?

A chest radiograph, while not necessarily the most useful imaging study, is obtained in almost every patient with respiratory complaints. The tracheal or carinal air column may demonstrate narrowing or axial distortion.

Computed tomography (CT), particularly multidetector computed tomography (MDCT), provides detailed information about the degree of stenosis, the length of the obstruction, involvement of adjacent vascular structures, and lymphadenopathy. MDCT provides a three-dimensional reconstruction of the airway lumen and a rough estimation of tumor length, although this technique does not replace the detail of endoscopic examination; early lesions may be difficult to detect even in experienced centerss, while MDCT of locally advanced tumors provides a fairly accurate measurement of axial extent. CT is useful in predicting vascular invasion, but it is unreliable in determining esophageal or submucosal tracheal invasion; the latter is commonly observed in adenoid cystic carcinoma.

The sequence of Figure 2, Figure 3, and Figure 4 show a large adenoid cystic carcinoma in a 24 year old woman. Gross tumor length may be measured by CT but the ability to perform a complete resection is difficult to predict as submucosal infiltration often extends beyond the gross mass.

Figure 2.

This 29-year-old patient with a four-year history of shortness of breath was found to have an adenoid cystic carcinoma of the trachea. The chest radiograph shows narrowing and distortion of the tracheal air column.

Figure 3.

This 29-year-old patient with a four-year history of shortness of breath was found to have an adenoid cystic carcinoma of the trachea. The three-dimensional reconstruction provides a left anterior oblique view of the narrowed tracheal air column.

Figure 4.

This 29-year-old patient with a four-year history of shortness of breath was found to have an adenoid cystic carcinoma of the trachea. The extratracheal tumor is seen in the coronal image.

Figure 5 and Figure 6 show CT images 3 (Figure 5) and 3 1/2 (Figure 6) years after right upper lobectomy. The images demonstrate subtle progressive thickening of the left tracheal wall that was missed at the first reading of the CT. Surveillance bronchoscopy for high-grade dysplasia at the bronchial stump led to the diagnosis of squamous carcinoma shortly after the second CT. At resection, the tumor was found to be transmural with invasion of a left paratracheal lymph node.

Figure 5.

Figure 6.

What non-invasive pulmonary diagnostic studies will be helpful in making or excluding the diagnosis of a tracheal tumor?

A diagnosis of high-grade tracheal stenosis may be suspected from a deformed flow-volume loop, but lung function studies rarely provide useful information for tumor management beyond diagnosis.

What diagnostic procedures will be helpful in making or excluding the diagnosis of a tracheal tumor?

Bronchoscopy provides the precise location of the tumor and an opportunity to assess the tracheal wall above and below the main lesion. Some tumors infiltrate the airway wall in the submucosa, while others show localized polypoid growth. To determine resectability, measurement of absolute tumor length as a proportion of overall tracheal length is important.

Fiberoptic endoscopes are the instruments used most frequently. Their use requires judgment, as the endoscope may obstruct the residual lumen in large tumors. Alternatively, rigid ventilating endoscopes provide an airway during the procedure and allow endoscopic resection to be performed using the bronchoscope itself. Endoscopic lasers should be applied with great care to avoid injury to the airway above and below the tumor before surgical resection.

Is endoscopic biopsy obligatory in every tracheal tumor? If a localized lesion obstructs the tracheal lumen, chances are that tracheal resection is required for complete removal. While not every tumor must be confirmed by biopsy, long, malignant lesions and those that appear unresectable require biopsy for treatment planning.

What pathology/cytology/genetic studies will be helpful in making or excluding the diagnosis of a tracheal tumor?

Routine histologic examination of tumor biopsies with selective immunohistochemical staining provides the diagnosis. The diagnosis of salivary gland tumors and their distinction from bronchogenic carcinoma sometimes requires specialized pathologic review. While the role of genomic tumor typing has not been defined for tracheal carcinomas, it should be considered for bronchogenic carcinoma.

If you decide the patient has a tracheal tumor, how should the patient be managed?

The patient with acute airway obstruction needs immediate attention, but the long- and short-term consequences of any sudden intervention must be carefully considered. First, humidification of inspired air is provided in order to thin respiratory secretions, and efforts are made to alleviate anxiety in order to decrease oxygen consumption and ventilatory rate. Helium admixture to the inspired air (Heliox) may decrease airway resistance, in which case the oxygen fraction should be kept below 0.3.

If urgent intervention requires general anesthesia, the use of muscle relaxation should be avoided until the airway is secured. The patient's own airway is likely to obstruct during muscle paralysis, forcing traumatic interventions that otherwise could be prevented. Endotracheal intubation in the event of clinical deterioration may be difficult, and small-bore endotracheal tubes (4, 5, and 6 mm) should be available. Awake intubation is not a suitable technique if the site and nature of the airway obstruction are unknown as it may provoke coughing and agitation; unless an experienced surgeon and anesthesiologist are at hand, general anesthesia is best avoided.

Urgent radiation may diminish the tumor burden, at the price of raising the risk of resection, as radiation impairs healing of tracheal anastomoses and increases dehiscence and stricture rate. Therefore, the determination of resectability should precede radiation except in the most unusual circumstances. If a surgeon with experience in the surgical management of tracheal tumors has declared the tumor unresectable, primary radiotherapy of radiochemotherapy may be instituted.

Inhaled, oral, or parenteral steroids have no role in the management of airway obstructions that are due to tracheal tumors. If the patient has been treated with oral steroids for a clinical diagnosis of asthma, steroids should be discontinued prior to any attempt at resection.

Treatment options consist of tracheal resection with end-to-end anastomosis; primary radiation of malignant, unresectable tumors; postoperative adjuvant radiotherapy for malignant, resectable tumors; bronchoscopic resection of luminal tumor; and tracheal stenting of malignant strictures not suitable for radiotherapy.

Tracheal resection with end-to-end anastomosis

Complete resection is the best treatment for benign tumors and localized malignant tumors; long-term survival has been observed after resection of tracheal carcinomas in numerous studies. Leaving positive microscopic margins after resection of all gross disease appears to be preferable to the excessive tension that results from overly radical resection. Positive microscopic margins also are an acceptable oncologic option for long adenoid cystic carcinoma, for example.

Laryngotracheal resection of tumors in or at the subglottic space preserves laryngeal function and immediately restores airway continuity in most patients, without the need for prolonged tracheal intubation.

At the carina, resection and reconstruction with or without pulmonary resection is a technically challenging operation. The operative risk increases with descending segments of airway from laryngotracheal to carinal resection. The factor of paramount importance in the success of carinal resection is the amount of tension at the anastomoses; surgical judgment and experience matter most.

Table 3 details the experience with primary tracheal squamous and adenoid cystic carcinoma at Massachusetts General Hospital over four decades. The resection rate rises and hospital mortality falls over time with increasing institutional experience. Modified from 15560996.

Table 3.

Evolution of surgical experience and mortality over four decades at Massachusetts General Hospital
Decade Total patients (n) ACC patients (n) SCC patients (n) Resections performed (n) Resection rate (%) Hospitalmortality (%)
1962-1971 19 7 12 13 68 21
1972-1981 54 29 25 33 61 11
1982-1991 107 54 53 71 66 5
1991-2001 88 43 45 72 82 3
Total 268 133 135 189 75 7

Primary radiation of malignant, unresectable tumors

Primary radiation may achieve effective palliation of airway obstruction, but reports of long-term survival are rare and are often related to the natural history of the disease, as in adenoid cystic carcinoma.

Postoperative adjuvant radiotherapy for malignant, resectable tumors

Radial margins at the surface of the tracheal wall and axial margins at the cut edge prepared for anastomosis are close to essential mediastinal structures in all but the earliest tumors. This proximity precludes resection according to radical oncologic principles. Adjuvant radiation with doses of 54 to 60 Gy is given routinely, based on extrapolation from the treatment of bronchogenic carcinoma with proximity to vertebral bodies or superior sulcus.

Bronchoscopic resection of luminal tumor

Endoluminal core-out of tumors is considered when temporizing or palliative restoration of airway lumen is required. While the procedure can be repeated, bronchoscopy is usually not employed for prolonged palliation. The core-out may be performed with biopsy forceps, the tip of the rigid bronchoscope, or a laser.

Tracheal stenting of malignant strictures not suitable for radiotherapy

Insertion of preformed silicone tracheal T-tubes for self-expanding metal stents may provide prolonged palliation of breathing in patients who malignant tracheal obstruction is suitably located. Expandable metal stents may erode into adjacent structures, and this risk is significant if survival is prolonged, as in adenoid cystic carcinoma. Tracheal T-tubes are unsightly because of the sidearm that exits in the neck, but their risk of erosion is low.

Although the role of adjuvant chemotherapy is unclear, combined primary or adjuvant therapy is often employed for bronchogenic carcinoma. Its role in the treatment of adenoid cystic carcinoma or tracheal sarcomas is not defined.

What is the prognosis for patients managed in the recommended ways?

The natural history of tracheal obstruction from benign or malignant primary tumors has not been adequately documented, primarily because patients who present with bleeding or neoplastic obstruction of the trachea undergo remedial procedures for symptom relief. However, without tracheal resection, and despite the presence of a patent airway, survival after diagnosis in tracheal carcinoma or sarcoma is short because of locoregional and distant progression. Survival after primary radiotherapy is limited, with the exception of adenoid cystic carcinoma, which has a slow progression.

The survival after resection of squamous cell carcinoma is related to depth of invasion, as demonstrated in Figure 7 and Figure 8. Increasing mural invasion lowers survival, and no long-term survival was observed in a small number of patients with thyroid invasion. However, existing experience supports tracheal resection as curative treatment for patients with tumor limited to the tracheal wall.

Figure 7.

Overall survival after resection of squamous carcinoma in 59 patients as a function of depth of invasion. Note poor outcome when tumor was present at the specimen surface of extended into the thyroid gland.

Figure 8.

The role of surgical treatment in adenoid cystic carcinoma was previously considered doubtful because most patients could not undergo tracheal resection with negative margins because of the marked submucosal infiltration well beyond the gross borders of these tumors. The advantage of resection with microscopically positive margins over primary radiotherapy was not obvious. However, because recent data suggest that long-term survival after resection and postoperative adjuvant radiotherapy surpasses that of primary radiotherapy, the pursuit of surgical therapy should be encouraged even if R1-resection with microscopic disease at the tracheal margin is the anticipated result.

The association of operative and histologic factors with long-term survival in 105 patients after resection of adenoid cystic carcinoma is shown in Table 4. Long-term survival of patients with microscopically positive tracheal resection margins is intermediate in duration between those with negative margins and those with grossly positive margins.

Table 4.

Overall disease-free survival after resection of tracheal adenoid cystic carcinoma divided by pathologic subgroups
Survival rate (%)
Mean survival
Pathological subgroup N (years) P-value 5-year 10-year 15-year 20-year
Airway resection margins
Grossly positive 8 8.2 * 55 27 27 0
Microscopically positive 50 13.7 77 65 45 34
Negative 47 19.2 85 69 62 51
Radial resection margins
Grossly positive 2 3.8 50
Microscopically positive 74 12.7 0.005 71 57 46 25
Negative 29 21.3 100 82 69 62
Extramural extent
Yes 85 13.9 0.018 74 60 45 30
No 20 23.0 100 82 82 72
Invading adjacent organ(s)
Yes 20 13.3 0.377 67 57 34 34
No 85 16.4 82 66 56 40
Perineural growth
Yes 35 10.7 0.014 64 36 24 24
No 12 20.1 91 91 91 78
Not noted in pathology report 58 17.5 86 73 58 39
Lymph node invasion
Yes 16 8.4 0.017 54 32 16 16
No 45 16.8 76 66 54 38
No lymph nodes sampled 44 17.5 94 77 73 55
Overall 105 16.0 79 64 53 40

Without treatment, benign tumors may lead to asphyxiation or postobstructive pneumonia, and longstanding obstruction may progress to bronchiectasis. Pneumonia or bronchitis are symptoms that deserve complete resection as treatment. Endoscopic core-out alone does not remove mural tumor and therefore does not replace resection.

What other considerations exist for patients with tracheal tumors?

In patients with suspected primary tracheal tumors, any intervention that limits later treatment options should be avoided before referral for potentially curative resection.

The treatment of tracheal tumors will exasperate the student of evidence-based medicine. Their incidence is so low that the level of experience gathered at individual centers has influenced and even determined the state of therapy. This concentration of experience is threatening to disperse as surgical graduates of these centers have taken up clinical management in increasing numbers after leaving their training programs. One advantage of this dispersal of experience may be an elevated general quality of surgical care for tracheal carcinoma.

The benefit of long-term survival after surgical resection of selected patients has been demonstrated at numerous institutions and is not controversial.

The rationale for postoperative adjuvant radiotherapy was originally borrowed from equivalent indications in lung cancers with proximity to the superior sulcus or vertebral bodies. The strenuous avoidance of preoperative radiotherapy relates to unavoidable tension on tracheal anastomoses after tumor resection; an anastomosis exposed to both radiation and tension has a high risk of failing by dehiscence, threatening the patient’s life in the early postoperative period. therefore, the treatment of primary tracheal tumors has evolved by experiential reasoning rather than dispassionate study. The results of therapy are satisfactory given these limitations.

What’s the evidence?

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