19

The average adult trachea is approximately 12 cm in length and 1.5 to 2.5 cm in width, and it is a hollow conduit connecting the larynx to the carina. It is divided in the proximal one-third cervical trachea and distal two-third thoracic trachea. Extension or flexion of the neck can either increase or decrease the amount of trachea above the sternal notch, respectively. There are 18 to 22 c-shaped incomplete cartilaginous rings, with each ring being approximately 4 mm in width and separated from one another by annular (intercartilaginous) ligaments. The trachealis muscle spans the length of the trachea, providing anterior and lateral support. This muscle is made of both longitudinal and transverse layers of smooth muscle. In addition, there is a posterior membranous portion of the trachea that separates the airway from the esophagus.1,2

The carina is approximately 38 cm from the incisors and is the bifurcation point of the trachea into the right and left main stem bronchi. It is held in position by the aortic arch. The right mainstem bronchus is more vertical, and this then divides into three upper, two middle, and five lower divisions. The left mainstem bronchus is further divided into two upper, two lingular, and four lower divisions.¹

The mucosa of the tracheal lumen is made of ciliated pseudostratified columnar respiratory epithelium that overlies areolar and lymphoid tissue with elastic fibers, blood vessels, nerves, and mucous glands. In smokers, the cilia are destroyed and squamous metaplasias of the epithelium can result.1

The blood supply to the trachea is segmental and travels from lateral to medial. The primary arterial inflow is from the inferior thyroid artery off the thyrocervical trunk. This supplies the upper trachea and esophagus through three branches with distal anastomotic connections from the superior thyroid artery off the external carotid artery. The lower trachea and carina are supplied by the bronchial artery off the descending thoracic aorta. In addition, transverse intercartilaginous arteries extend into the tracheal wall and branch into the submucosa. This segmental blood supply can be easily violated and may lead to tracheal necrosis if extensive dissection along a significant length of the trachea is undertaken.^1,3

Lymphatic drainage of the trachea is to the paratracheal, pretracheal, and subcarinal lymph nodes, with the primary echelon of nodes being closest to the tumor itself. It is rare for “skipped” nodal metastasis to occur.¹

Surrounding the trachea are vital structures including the esophagus, thyroid gland, parathyroid glands, recurrent laryngeal nerves, great vessels, aorta, skeletal muscles, and other soft-tissue structures. These structures can often be the source of secondary tumors or can be directly invaded by primary tumors of the trachea.¹

Diagnosis

Clinical Presentation

A high index of suspicion is required to diagnose primary tracheal malignancies as they often present with nonspecific signs and symptoms. In a series of 74 patients with primary tracheal malignancies treated at MD Anderson Cancer Center (MDACC), the most common presenting symptoms were most frequently dyspnea (55.4%), hemoptysis (48.6%), cough (41.9%), and hoarseness (35.1%).⁴ Other presenting symptoms included dysphagia (28.4%), weight loss (30%), stridor (18.9%), sore throat (13.5%), history of asthma (6.8%), and wheezing (4.1%). Similarly, in a series of 270 patients with primary squamous cell carcinoma (SCC) and adenoid cystic carcinoma (ACC) of the trachea treated at Massachusetts General Hospital (MGH), the most common presenting symptoms were dyspnea and cough.⁵ This group also noted that patients with SCC tended to present with hemoptysis. Unfortunately, in many cases, these symptoms were wrongfully attributed to adult-onset asthma or chronic obstructive pulmonary disease, thereby delaying diagnosis.^4,5 Furthermore, patients may not experience significant symptoms until 50 to 70% of the luminal diameter of the trachea is narrowed (Fig. 19.1A). In addition, exertional dyspnea and dyspnea at rest may not develop until the trachea has narrowed to less than 8 and 5 mm, respectively.^6,7

Pulmonary function tests can detect obstruction in the upper airway and identify flow-volume loops that have characteristic flattening of both inspiratory and expiratory phases, providing further evidence of a fixed upper-airway obstruction.²

Imaging

Imaging studies are critical in the diagnosis and work-up of primary tracheal malignancies. These studies play a key role in depicting these tumors and assessing tumor extent within the tracheal lumen, airway wall, and surrounding structures before treatment planning.⁸ Unfortunately, plain chest radiographs are often unremarkable in the setting of tracheal malignancies, although airway compression, tracheal narrowing, and postobstructive findings may be noted.

Thin-section contrast-enhanced computed tomography (CT) of the chest is the diagnostic imaging modality of choice for the evaluation of tracheal tumors. Furthermore, the development of multidetector CT scans has resulted in excellent axial source images and aided multiplanar three-dimensional (3D) reconstructed images. These high-resolution images allow the clinician to better delineate complex airway anatomy and tumor morphology.^9–11 A CT is usually performed at full inspiration but can be performed at the end of or during expiration to study the dynamics of the airway and the affect of a tumor on the distal airways and lung parenchyma.⁸

Although individual tumor histologies may show subtle differences, CT findings associated with tracheal neoplasms include a polypoid intraluminal mass of soft-tissue density with irregular, smooth, or lobulated contours (Fig. 19.1B). Eccentric narrowing of the airway or circumferential wall thickening of the trachea creating localized stenosis can also be evaluated by using CT, as well as tumor extension through the tracheal wall and into the surrounding structures in the neck and mediastinum (Figs. 19.1B and 19.2A, B).⁸ CT with intravenous contrast is also the study of choice for the evaluation of suspected nodal metastases.

Several authors have studied the benefit of positron emission tomography (PET) in the evaluation of tracheal tumors.^12,13 Specifically, PET and fused PET/CT images are useful in differentiating malignant from benign tumors of the trachea. Park et al found that SCC often demonstrates high standardized uptake values (SUVs) while ACC and other salivary gland malignancies show variable uptake depending on the grade of differentiation.¹² Benign neoplasms of the trachea will typically demonstrate decreased SUV. PET and PET/CT may also be helpful in diagnosing patients with suspected secondary malignancies or distant metastases, as well as in the evaluation of residual or recurrent disease after treatment. Current literature suggests using PET imaging no sooner than 8 weeks postradiation because of the increased risk of false-positive results if performed earlier.¹⁴

The routine use of magnetic resonance imaging (MRI) has no significant advantage over present-day CT images except in the face of ACC. For these tumors, MRI offers superior evaluation of the surrounding soft tissue and extent of tumor involvement.2

Additional work-up for patients with tracheal tumors may include direct laryngoscopy and esophagoscopy, barium esophagram to evaluate the patency of the esophagus or the presence of a tracheoesophageal fistula, endoscopic ultrasonography, and fluoroscopy of the trachea and larynx to assess dynamic motion of these structures.¹⁵

Endoscopy

Bronchoscopy is an essential component in the diagnosis and work-up of patients with tracheal malignancies. While both flexible and rigid bronchoscopies allow for excellent visualization of the trachea and bronchi, rigid bronchoscopy is often preferred in the setting of airway compromise. Rigid bronchoscopy can be both diagnostic and therapeutic and allows for biopsy of tracheal lesions, dilation of a compromised airway, and ventilation.¹⁶ Several scopes of different diameters and lengths should be available when planning endoscopy and airway intervention in a patient with suspected tracheal cancer.

Another novel imaging modality is virtual bronchoscopy (VB).^17,18 This technique is noninvasive and uses CT scan images along with commercial software to examine 2D and 3D anatomic details. Images from multiple directions are created with extreme precision to adequately view intraluminal and extraluminal pathology. It has also proven to be useful in determining airway patency distal to the lesion, evaluating the length of airway stenosis, as well as helping to establish the feasibility of endobronchial procedures including dilations, stent placements, and laser ablation. The main limitation of VB is in its inability to adequately evaluate the mucosal surface of the respiratory tract. More specifically, mucosal irregularity, color, or friability cannot be assessed; thus, using VB for routine surveillance is not warranted. There is promising research that suggests that new aerosolized contrast agents or spectroscopic techniques can potentially differentiate between benign and malignant mucosal tissues within the respiratory tract, thus enhancing the sensitivity and specificity of VB to diagnose preinvasive cancers.¹⁸

Tracheal Neoplasms

Close to 90% of primary tracheal neoplasms in adults are malignant. However, most malignant neoplasms of the trachea are secondarily due to direct extension from laryngeal, thyroid, esophageal, bronchogenic, or other metastatic tumors.^19,20 In children, nearly 70% of tracheal neoplasms are benign.²¹ Table 19.1 outlines a variety of primary neoplasms, both benign and malignant, of the adult tracheobronchial tree.

Benign Tracheal Neoplasms

Although this chapter focuses on malignant tracheal lesions, it is noteworthy to know that approximately 10% of adult primary tracheal tumors are benign.¹⁹ The most common benign tumor is squamous papilloma caused by the human papillomavirus. Other benign lesions include pleomorphic adenoma, granular cell tumor, and benign cartilaginous tumors.

Table 19.1 Classification of Primary Tracheobronchial Tumors

Malignant Tracheal Neoplasms

SCC makes up the majority of primary tracheal malignancies, accounting for 36 to 59% of primary tracheal malignancies in most large series.2,4,5,19,22 Primary tracheal SCC is associated with smoking, has a male predominance, occurs in the sixth and seventh decades of life, and has a propensity for regional nodal metastasis.² Macroscopically, SCC appears as a large mass within the central airways with either exophytic or ulcerative component. It can be multifocal in approximately 10% of the patients, but majority of SCCs will occur in the distal trachea.⁸ Regional extent into the esophagus or mainstem bronchus is frequent.

Primary tracheal SCC is associated with worse outcomes compared with other tracheal malignancies, with overall 5-year survival rate ranging from 7.3 to 39%.⁵ It is well established that surgical resection is the mainstay of the treatment for SCC and resectabilty affords patients’ improved disease-specific and overall survival. A landmark study by Gaissert et al demonstrated that mean survival time was 38 months for resected tracheal SCC and 8.8 months for unresectable tumors undergoing chemotherapy and radiation.⁵ This study also demonstrates that locoregional recurrence is the main determinant of disease-specific survival in patients with tracheal squamous cell cancer.⁵

A study by Honings et al from MGH demonstrated specific pathologic features of primary tracheal SCC that may serve as prognostic predictors of survival.²³ On the basis of a histologic review of 59 resected tracheal SCC specimens, they identified completeness of resection, involvement of the thyroid gland, and lymphatic invasion as predictors of survival.²³ Although patients with well-differentiated tumors had a better overall survival than those with moderately or poorly differentiated tumors, this difference did not achieve statistical significance. This study emphasizes the importance of clear surgical margins and suggests that the invasion of the thyroid gland may preclude a surgical cure.²³

Adenoid Cystic Carcinoma

ACC represents the second most common primary tracheal malignancy. In a large observational study by Urdaneta et al, ACC accounted for 16.3% of tumors.²⁴ In other series, ACC represents up to 40% of all tracheal malignancies.^2,4,5,19,22 It has been shown to occur equally in males and females and presents most commonly in the fifth decade of life.²⁵

ACC is an aggressive malignancy of salivary gland origin that is characterized by local invasion and perineural spread. Almost half of tracheal ACCs are found in the proximal trachea, with the most common presenting symptoms being dyspnea, cough, and hoarseness. Because of the later findings, patients are often referred to an otolaryngologist first.²⁵ These tumors tend to be locally recurrent, particularly with inadequate surgical margins (Fig. 19.1). Nodal and paratracheal metastases develop late in the course, with distant metastases occurring in the lungs, liver, or bones. Unlike SCC of the trachea, smoking is not associated with the development of ACC. Also, in contrast to SCC, the prognosis for resected ACC is much better with 5- and 10-year survival rates of 52 and 29%.⁵ Although surgery is the mainstay of the treatment for this malignancy, other modalities have been investigated and are discussed in the “Management of Tracheal Malignancies” section.

The remaining 30% of primary tracheal neoplasms are a heterogeneous group of epithelial, salivary, and mesenchymal tumors.^19,20

Pediatric Tracheal Malignancies

In contrast to adult patients, the vast majority of pediatric tracheal tumors are benign.²¹ Primary tracheal cancers arising in children are extremely rare, with only 14 cases reported in the literature.²¹ There is often a significant delay in diagnosis, as the early symptoms are wrongfully attributed to asthma or upper airway infection. Romão et al published their experience with two cases of tracheal cancer in children and performed a literature review.²⁶ Mucoepidermoid carcinoma accounted for the majority of these cancers, and when complete surgical resection was feasible, the prognosis was generally good. The average age at presentation among the cases reviewed in this study was 7 years, and the delay from the onset of symptoms to diagnosis ranged from 2 weeks to 2 years.²⁶

Secondary Tracheal Malignancies

Secondary malignancies of the trachea arise as a result of either direct invasion or metastasis and are more common than primary tumors.^19,20 A wide variety of metastatic tumors have been described in the trachea, most commonly from thyroid malignancies; however, SCC from other sites in the head and neck, esophageal carcinoma, melanoma, sarcoma, tumor of breast, and colorectal tumor are also known to invade the trachea.

Thyroid cancer is the most commonly invasive tumor of the trachea. Aerodigestive tract invasion has been reported in approximately 7 to 16% of all cases of thyroid carcinoma.²⁷ Although anaplastic thyroid cancer is often associated with tracheal invasion, a study of patients with thyroid cancer with tracheal invasion by Gaissert et al demonstrated that 76% of tumors were well-differentiated carcinomas.²⁷ Sites of invasion include all portions of the endolarynx, trachea, esophagus, strap muscles, and recurrent laryngeal nerve.²⁸ While the prognosis of well-differentiated thyroid cancer is excellent, laryngeal or tracheal invasion is an independent predictor of death.^27,29 McConahey et al found that laryngotracheal invasion was the direct cause of death in 36% of the patients with locally advanced thyroid cancer.³⁰

Controversy exists regarding the extent of resection required to treat thyroid cancer with tracheal invasion. Several authors recommend radical complete resection irrespective of the degree of invasion to be the most oncologically sound procedure.^31,32 However, many authors have demonstrated no difference in survival for patients with locally invasive well-differentiated thyroid carcinoma treated by radical resection of aerodigestive tract structures and those treated by near-complete conservative surgery.28 Czaja and McCaffrey found no difference in survival for patients undergoing shave excision versus radical resection if gross tumor did not remain.²⁹ Although there is debate regarding the extent of resection, there is generally agreement on the need for radical resection when tracheal mucosa has been invaded.

Staging

An official staging system for primary tracheal malignancies has not been universally adopted to date by the American Joint Committee on Cancer. However, a TNM (tumor, node, metastasis) staging system (Table 19.2) developed by Bhattacharyya is widely accepted and validated.³³ He proposed a TNM system for primary tracheal malignancies, in which T1 and T2 tumors are limited to the trachea and differentiated by size of less than or greater than 2 cm. T3 tumors have spread outside the trachea without invasion of adjacent structures, while T4 tumors have invaded adjacent structures or organs. Unlike other sites in the head and neck, regional nodal disease is defined as the absence (N0) or presence (N1) of metastatic lymph nodes. Overall stage is defined as follows: stage I, T1N0; stage II, T2N0; stage III, T3N0; stage IV, T4N0 or any N1 disease.³³

Management of Tracheal Malignancies

Surgery

Surgery for primary tracheal cancer may involve acute surgical management for tracheal obstruction as well as definitive surgical resection. According to Grillo, therapeutic goals of the initial emergent management of tumor-related obstruction are as follows: (l) to facilitate safe anesthesia for resection; (2) to permit delay of resection for study, to clear obstructive pneumonia, to wean from high doses of steroids, and to stabilize medical conditions; and (3) to allow palliative irradiation, external or brachytherapy.³⁴ If obstruction is due to extrinsic compression by a tumor, an internal stent or Y-tube stent can provide temporary relief (Fig. 19.2).^35,36 Blockage by a tumor must be removed rather than dilated.³⁴

Table 19.2 Primary Tumor and Nodal Staging for Tracheal Carcinoma

Adapted from reference 33.

Surgical resection is the primary treatment modality in most cases of primary tracheal malignancies and is the only modality that has consistently demonstrated the potential for cure and long-term survival.^2,5,11 In addition, it is the primary treatment modality for benign tumors of the trachea. In a large study by Gaissert et al, it was demonstrated that those patients undergoing surgery had better overall survival than those treated by other modalities.⁵ They also reported that disease-free survival was longer in patients who had complete resection than in those whose resection was incomplete (p < 0.05), in those with negative airway margins than in those who had positive airway margins (p < 0.05), and in patients with adenoid cystic histology compared with patients with squamous histology (p < 0.001).^2,5

It is important to note that resection requires multidisciplinary collaboration between head and neck surgeons, thoracic surgeons, and skilled anesthesiologists because of the inherent danger associated with airway manipulation. Acute and long-term operative complications should also be considered.

Contraindications for surgery include greater than 50% involvement of the adult trachea or 30% involvement of the juvenile trachea, extension to vital surrounding structures, extensive nodal involvement, metastatic disease, or a mediastinum that has received radiation dose of more than 60 Gy or has been operated on.² In addition, patients should have a proper medical evaluation preoperatively, as these procedures are high-risk and preexisting medical conditions can preclude the operation.

Anesthesia

When performed surgery on the airway including the larynx, trachea, and bronchi, it is crucial to have an anesthesiologist who is skilled in managing these complex cases. It is not infrequent to have patients in respiratory distress, and urgently establishing a secure airway is of utmost importance, which must be done in a timely manner. Use of inhalation agents, slow induction of anesthesia, and maintaining spontaneous ventilation with the initial avoidance of muscle relaxants maybe necessary in several of these cases.³⁷ The use of jet ventilation has been well established in various airway surgeries, and as such, it has a critical role in procedures performed on patients with endoluminal disease.^38,39 A catheter is placed beyond the lesion to provide ventilation to the distal airways. However, care must be taken to allow egress of gas and to prevent breath stacking, which can lead to barotrauma.³⁷ Another option is cardiopulmonary bypass for extensive intrathoracic tracheal and vascular surgery.