Tracheal Neoplasms
Ann Marie Visosky , M.D.
November 4, 2004

Good morning. This morning I will be discussing primary tracheal neoplasms. I will start with an introduction and go on to a case presentation, discuss relevant anatomy, signs and symptoms, radiographic studies, the two most common types of tracheal neoplasms, and then we will go over treatment options.

The first report of a tracheal tumor dates back to 1762. They are quite rare tumors accounting for less than 1% of all malignancies and less than 0.1% of cancer deaths each year. There are approximately 2.7 new cases per million per year. Because they are so rare, we must have a high index of suspicion. Often these patients get diagnosed with adult onset asthma due to their symptoms and, because they are so rare, there is a limited amount of studies on tracheal tumors.

Our patient is a 41-year-old woman who was seven months pregnant with her sixth child when she began to experience symptoms of shortness of breath and dyspnea on exertion, dating back to the spring of 2003. She was initially treated for reactive airway disease by her primary doctor; however, her symptoms continued to worsen. She reported no prior medical problems, and her physical exam did not reveal any cause for her symptoms. A CT scan was obtained that showed a soft tissue mass in the mid to distal trachea region with 70% occlusion. She underwent a rigid bronchoscopy, and this revealed an obstructing lesion coming off the posterior trachea that was located about the distal one-third of the trachea. A biopsy at that time reported adenoid cystic carcinoma versus pleomorphic adenoma, and she was followed clinically for the remainder of her pregnancy. She had serial CT scans that were performed in July and December of 2003. They noted a patent airway. There was some mucosal thickening in the distal trachea, but she was doing well and had no recurrence of symptoms. She underwent a repeat bronchoscopy in January of this year, and the pathology at this time came back adenoid cystic carcinoma. Options for treatment were presented to the patient. She underwent evaluation for possible resection and radiotherapy, and the recommendation was given to her that she should undergo surgery. She chose instead to be followed clinically and has been followed up in clinic every couple of months, as well as she had a repeat CT scan in August of this year that noted no tracheal mass, and she did have one borderline anterior tracheal lymph node. She was seen in Clinic a couple of weeks ago and remains asymptomatic. The plan is for repeat bronchoscopy in January of 2005 for further evaluation. Now, in talking to the patient a couple of weeks ago, she went over her medication list with me and reported that she has turned to some alternative medicine and vitamins, has undergone a special diet, and turned to her spiritual faith for healing as well. This list to the side is the list of vitamins and medications that she is currently taking. In looking those up, most of them are presumed detoxifiers and are supposed to help boost the immune system.

Now the average length of the trachea is 11 cm from the inferior border of the cricoid cartilage to the carina and this varies with age, sex, and race. The side-to-side diameter is approximately 2-2.5 cm, and there are 18-22 cartilaginous rings present in the adult trachea. As we age, the angle between our sternum and trachea increases, and this may increase even more with kyphosis. The trachea becomes located further posterior in the mediastinum and can be difficult to expose. In the normal anatomic position, approximately half of the trachea is in the thoracic cavity, and the other half is above the thoracic inlet. Regarding the vascular supply, the inferior thyroid artery is the major source for the cervical trachea. In the thoracic trachea, a combination of vessels from the innominate and the subclavian artery is the main supply, and the distal end comes from bronchial arteries. All of these arteries come in laterally, and it is this arrangement of the blood supply that allows for anterior and posterior mobilization during surgery.

The clinical presentation of patients with tracheal neoplasms is variable. In most series, dyspnea is the most common complaint; but coughing, hemoptysis, asthma, and stridor can also all be found. It is much rarer to have symptoms related to involvement of adjacent structures such as hoarseness and dysphagia. Hemoptysis is more prevalent when it is squamous cell carcinoma and wheezing and stridor are often the symptoms that occur with adenoid cystic carcinoma, which is why a lot of these patients get treated for adult onset asthma. On physical exam, you can sometimes even hear a sternal murmur or wheeze with changes in position as the mass obstructs airflow.

Given the presenting symptoms of most patients, their initial radiographic study is a chest x-ray. It usually shows normal lung fields, and less than half were diagnosed with a tracheal neoplasm by chest X-ray; but there are some clues that can help detect the presence of a tracheal tumor, and these include tracheal narrowing, post obstructive atelectasis or pneumonia, and any abnormal calcifications in the area. Planer tomography was utilized before the advent of CT scans, and this is accomplished by the simultaneous motion of the radiograph tube and the film cassette with visualization of the selective layers of tissue. The motion intentionally blurs the surrounding structures, which allows for visualization of the area of interest. These were much more sensitive than standard chest x-rays, but currently CT is the imaging modality of choice. Spiral or helical CT scans are best, and 3D reconstructions are quite helpful. MRIs are not used very much, but in recent time they have been used a slight bit more to be applied to tracheal tumors to better evaluate the extension into tissue planes, mediastinal invasion, and vascular anatomy. Bronchoscopy is an important diagnostic tool. It allows for identification of the obstruction, biopsy for tissue diagnosis and, for benign or small lesions, allows removal endoscopically with lasers.

Approximately 80% of tracheal tumors are malignant, and the great majority of these are either adenoid cystic carcinoma or squamous cell carcinoma. There are conflicting reports in the literature as to which is the most common. In the three largest case series of surgically treated malignant tracheal tumors, adenoid cystic carcinoma is the most common; however, if all surgical and non-surgical cases are included, the highest incidence appears to be with squamous cell carcinoma.

Because of the rarity of these tumors and varied types and biological behavior of them, there are few large series in the literature. Long-range results of treatment of any specific type of tracheal neoplasm are difficult. I am going to discuss some features of the two most common malignant primary tumors and review information from the three largest case series available. The first by Pearlman and colleagues is out of Canada and that was reported in 1984. Grillo and Matheson in 1990 from Massachusetts General Hospital had a series that was over 26 years and that encompassed 198 patients, and then there was a large retrospective review out of France that was a multi-center case series and that had 208 patients and that was over 30 years.

Adenoid cystic carcinoma was formerly called cylindroma. It occurs equally in men and women and does not appear to have any correlation with smoking. The average age of the patient is usually in the 50s, but it has been seen in patients ages 30-70, and approximately half of adenoid cystic carcinomas appear in the proximal trachea. Tumor location has been correlated with prognosis, and there seems to be a worse prognosis in patients that have a mass that is quite distal, but this may likely be to the difficulty of resection in this location. Studies have shown that adenoid cystic carcinomas of the trachea appear to behave in a similar biological fashion as those of the salivary glands. It has a very prolonged clinical course, and the average time in the three series that I mentioned is about 51 months to recurrence. Grillo and Matheson report one patient that did not have a recurrence until 17 years later. It spreads most commonly by direct extension, submucosal, or the hallmark of adenoid cystic perineural invasion. Hematogenous spread is also seen and of those with hematogenous spread 50% of the time the metastasis is to the lungs. Patients with pulmonary metastasis may remain asymptomatic for multiple years, and the finding of a pulmonary metastasis on initial diagnosis does not necessarily preclude someone from having surgical therapy. Microscopic level of invasion is much greater than on gross inspection and frequently, on histologic examination, there are tumor cells found about 1 cm or more beyond the palpable and visible confines of the tumor. In gross appearance, an adenoid cystic tracheal neoplasm may be smooth, firm, well circumscribed, or some have reported poor margins. Although lymph nodes immediately adjacent to the trachea may be involved by metastatic tumor, this is less common than for squamous cell carcinoma. Histologically, adenoid cystic carcinoma on H&E stain as dark cells with solid and cystic ports. Maziak and colleagues, which include Pearson out of Toronto, put out a separate paper in 1996 that looked specifically at the patients in their series who had adenoid cystic carcinoma. They included the patients from their original data series in 1984 and extended it through 1995, which added another ten patients to their database. So this study was over a 32-year period. They saw a total of 38 patients with adenoid cystic carcinoma of the trachea in this timeframe, and 32 of them were treated with resection and reconstruction. Twenty-six of the 32 received adjunctive radiotherapy and six received radiotherapy alone. None had clinical evidence of distant metastasis at the time of diagnosis. The mean survival for the entire group of 38 was 85 months, and those with presumed complete resection showed a mean survival of 9.8 years versus those with incomplete resection who showed a survival of 7.5 years. The majority of these also had adjunctive radiotherapy. So they showed a trend towards a slight better survival, but this was not statistically significant; however, if you look at the ten-year mark, 69% of those with presumed complete resection were still alive while only 30% of those with incomplete resection were still alive. Now this differs from squamous cell carcinoma of the trachea where the best prognosis is if you can achieve complete resection. Now the authors of this study do feel, however, that adjunctive radiotherapy is beneficial, and they note that for a good number of their patients they had not been post resection for a long enough period of time to be able to make very many conclusions about the benefit or not having a benefit to radiotherapy.

Now with squamous cell carcinoma, the peak incidence is in the 50s with the average age in the 60s, and it is most common in men. The majority of patients do have a smoking history. It is common to have preceding or subsequent primary neoplasms in the respiratory or digestive tract with tracheal squamous cell carcinoma. Of the 48 patients seen at Mass General in Grillo and Matheson’s study, 40% had either previous history or another squamous cell carcinoma in the aerodigestive tract. It may present as an exophytic lesion that is circumscribed or as a spreading lesion in the trachea. Ulcerative presentations are also reported, and metastasis to paratracheal and subcarinal lymph nodes and direct invasion of mediastinal structures can occur.

Now this chart is from Grillo and Matheson’s series of their 198 patients, and 48 of these patients had primary lesions that were other than adenoid cystic or squamous cell. The most common benign lesion in their series was squamous papillomas, and those of intermediate malignancy were carcinoid tumors. They had ten patients with carcinoid tumors. These usually have a benign course as compared to the more aggressive atypical carcinoids, and the cells are capable of secreting active peptide hormones as with carcinoids in other parts of the body, but carcinoid syndrome is quite rare with tracheal tumors. Most of these tumors present with obstructive type symptoms. Four patients in their study also had mucoepidermoid carcinoma, and the remainder were rare tumors that oftentimes only were seen in one patient in the series.

The first tracheal resection with primary anastomosis occurred in 1957, and in 1964 Grillo and colleagues modified tracheal surgery and began to popularize it. Today, optimal therapy for primary airway lesions that are deemed resectable is surgical resection and reconstruction. The general principles that allow for success for such a surgery as described by Pearson and colleagues include an accurate preoperative identification of the exact level and length of the lesion to be resected, and this is achieved through imaging and often preop bronchoscopy evaluation. Resection has to be through healthy tissue, and tracheal circulation must be maintained. Dissection of areas not to be resected should be limited, and there should be no tension on the anastomosis. For tumors that present in the upper half of the trachea, an anterior collar incision placed low in the neck is used. Midtracheal tumors are approached through a partial or complete median sternotomy extended down from the collar incision. Pearson and colleagues advocate a median sternotomy approach for lower tracheal tumors as well including the carina because it allows for access to the entire airway through one incision and gives the surgeon the ability to mobilize the trachea throughout its length giving good access for release maneuvers. Grillo and colleagues perform a right posterolateral thoracotomy for lower tracheal and carinal tumors and the operations need to be planned flexibly so that the surgeon, if needed additional exposure due to positive margins, is capable of getting more tension free release of the trachea. The technical detail of each, however, is the same.

Maneuvers have been devised in order to reduce anastomotic tension in intrathoracic reconstructions. Now one of the easiest and quite beneficial is actually just neck flexion of the patient. Superior mobilization of the distal trachea from the thorax was first described in 1965 by Grillo. Super hyoid laryngeal release, division of inferior pulmonary ligament, and hilar release, and rarely indicated division and reconstruction of the carina are all other possible maneuvers. Laryngeal release may provide about 1-3 cm anteriorly where the maximum amount of relaxation is needed, but this is not as helpful with distal tracheal or carinal resections. Before the 1960s, it was believed that the maximum number of tracheal rings that could be resected and primary reconstruction performed was four rings. Now as I mentioned, it was in the 60s and 70s that major progress occurred in tracheal surgery. With the advent of better surgical techniques came the idea of using prosthetic material to replace the resected tracheal cartilage. Today prosthetic reconstruction still remains limited. In most patients, the current mobilization techniques that I described permit enough mobilization to allow for primary anastomosis. In those rare patients that it does not, Pearson and colleagues recommend using a heavy duty porous material such as Marlex mesh, but they recommend that it be enveloped in a layer of omentum and that the overlying segment of the innominate artery be resected because just having tissue there alone does not prevent fistula, which is a complication seen in many of the early prosthetic reconstructions. As short a prosthesis as possible should be used in order to improve the chances of endoluminal epithelialization and to avoid later stenosis.

Surgical complications of resection and primary anastomosis that we should be aware of and that may require some ENT intervention include anastomotic stenosis, suture line granulomas—although these were more common before absorbable sutures—esophageal fistulas, vocal cord paralysis, especially if extensive dissection was required, aspiration on deglutition, principally after laryngeal release. Now in Grillo and Matheson’s series, they note that most cases resolved over time.

Now regarding radiotherapy, due to the narrow margins that are often obtainable in tracheal reconstruction, even when margins and lymph nodes are histologically negative, Grillo and Matheson feel that it is prudent to have their patients undergo postoperative radiation for both squamous cell carcinoma and those with adenoid cystic carcinoma of the trachea. They allow a one-month recovery time from surgery before radiation is started. Both squamous cell carcinoma and adenoid cystic carcinoma of the trachea are sensitive to radiation, with adenoid cystic carcinoma being quite sensitive. In the series from Grillo and Matheson in 1990, their doses varied from 45-60 Gy. Most would agree that radiotherapy alone should only be reserved for those patients with nonresectable disease. Approximately 54-60 Gy are usually delivered and some studies have even shown 60-70 Gy are needed to achieve full tumor regression, but there is a great amount of damage to normal tissue at these high radiation levels.

Regarding chemotherapy, it does not play a standard role in the treatment for tracheal neoplasms. Adenoid cystic carcinoma with its relatively low growth rate has almost a nonexistent response to chemotherapy, and those studies that have been conducted looking at platinum-based combinations for the most part included adenoid cystic carcinoma of the salivary glands or of the head and neck region, and there is a very wide varied range of response shown in these studies. So, as for now, there is really no good data to indicate that it is beneficial.

So, in summary, we have to remember to have a very high index of suspicion for these lesions because they are so rare. The majority are malignant, and adenoid cystic carcinoma and squamous cell carcinoma are the most common. Because of the limited amount of information that is available, we really have to manage each patient on an individual basis, and surgical resection remains the greatest chance for a cure. Postoperative radiation is recommended even if margins are negative and long-term follow-up is necessary, especially for adenoid cystic carcinoma given its prolonged clinical course.

Case Presentation

The patient is a 41 year-old, Caucasian woman who at presentation was 7 months pregnant with her 6 th child. She had begun experiencing shortness of breath, and dyspnea on exertion 3 months prior in the early 2003. She had been treated for reactive airway disease; however, her symptoms continued to worsen. Her physical exam did not reveal any obvious cause for her symptoms.

A CT scan of her neck and chest was performed that demonstrated a soft tissue mass in the mid to distal trachea with ~ 70% obstruction of her airway. She underwent a rigid bronchoscopy with removal of the obstructing lesion. The biopsy of the lesion was reported as adenoid cystic carcinoma vs. pleomorphic adenoma. Her symptoms were relieved and she was followed clinically during the remainder of her pregnancy. Post partum, serial CT scans were obtained in July 2003 and December 2003. The chest CT scans noted a patent airway with some mucosal thickening in the distal trachea. She was asymptomatic. The patient underwent a repeat bronchoscopy in January 2004. Biopsy of a small mass in the same area was reported as adenoid cystic carcinoma. Treatment options were discussed with the patient. She underwent evaluation by cardiovascular surgery and radiation therapy for possible resection and radiotherapy. Recommendations were made for primary resection and possible radiotherapy. The patient chose against surgery and wanted clinical follow up. She is currently participating in alternative medical therapies and vitamin supplements and follows a special health diet. A repeat CT scan in August 2004 indicated no tracheal mass; a borderline anterior tracheal lymph node was noted.

The patient was seen in clinic 2 weeks ago. She is feeling well and is asymptomatic. The plan is to perform a repeat bronchoscopy in 3 months for re-evaluation and close monitoring.

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