Upper airway tumors encompass a wide variety of epithelial and soft tissue neoplasms that are relatively rare and usually malignant. Squamous cell and adenoid cystic carcinomas are the most common. Definitive diagnosis is often delayed because the symptoms associated with upper airway tumors are similar to those of more common pulmonary disorders such as chronic obstructive pulmonary disease. Although less invasive palliative treatment modalities are available, surgical resection with airway reconstruction usually offers the best chance for an excellent long-term prognosis. Figure 60-1 shows the normal upper airway anatomy.

Neoplasms can arise from any of the tissues present in the trachea and mainstem bronchi. These tissues include the columnar ciliated mucosa, the submucosa (which contains a significant number of mucous glands), cartilage, and connective tissues. Accordingly, the types of upper airway tumors are numerous (Table 60-1). Tumors are classified as benign or malignant and epithelial or soft tissue in origin. Lesions are evenly distributed throughout the length of the trachea.

In adults, most upper airway tumors are malignant.^1–4 Extremely rare, their incidence is much lower than carcinomas of the larynx and lung. In fact, upper airway tumors account for fewer than 0.2% of all respiratory tract malignancies.⁵ The malignant epithelial tumors squamous cell carcinomas (SCCs) and adenoid cystic carcinomas (ACCs) are the most common primary tracheal malignancies, followed by carcinoid and mucoepidermoid carcinomas.^1–4,6–12 Benign tumors represent a wide variety of histologic types. The most common are squamous papilloma, pleomorphic adenoma, and benign cartilaginous tumors.³

Squamous Cell Carcinoma

Although SCC usually occurs in lobar and segmental bronchi, it is the most common neoplasm of the trachea and mainstem bronchi.^3,8,13 SCC of the trachea occurs most commonly in males between the ages of 50 and 70 years and is associated with cigarette smoking.^2,3,14 SCC has papillary and basaloid variants and usually appears as a well-localized, exophytic, ulcerated lesion. SCC also can occur as a focally invasive component of a squamous papilloma. The cancer may spread to regional tracheal lymph nodes and directly into mediastinal structures. Approximately one-third of patients have infiltrative local extension and mediastinal or pulmonary metastasis at the time of diagnosis.⁶

Adenoid Cystic Carcinoma

ACC, a salivary gland type, is the second most common primary upper airway malignancy.^3,8,13 The mean age for patients with tracheal ACC is 44 years.¹⁵ ACC appears to be unrelated to smoking and is evenly distributed between males and females.^3,7,14 These neoplasms, which can have cribriform, tubular, or solid histologic features, generally have a much slower growth pattern and more insidious onset than SCC. Although histologic pattern is important, prognosis appears to be more a function of disease stage.¹⁶

ACC growth patterns are either nodular, infiltrative (in which the tumors grow submucosally without producing a distinct mass), or of mixed nodular and infiltrative type.^7,17 Tumors can spread along the airways and involve a long length of trachea by submucosal and perineural spread without involving adjacent mediastinal structures.¹⁵ The microscopic level of invasion often exceeds that which is grossly apparent. Negative resection margins can be difficult to achieve, although long-term disease control has been reported with positive surgical margins.^2,15 Tumors also can spread radially into adjacent parenchyma and lymph nodes. These tumors tend to displace rather than invade mediastinal structures.¹⁷ Approximately 10% of ACC metastasize to regional lymph nodes.^3,12,14 When these tumors metastasize, they locate predominantly in the lung, bone, and liver. Patients can have extended survival despite the presence of pulmonary metastases, which tend to progress very slowly.^1,15

Carcinoid Tumors

Carcinoid tumors are malignant neuroendocrine tumors that make up to 4% of all primary lung tumors.^18,19 Although most bronchial carcinoid tumors arise in lobar bronchi or the lung periphery, 10% originate in the mainstem bronchi.²⁰ Carcinoid tumors appear as fleshy, highly vascular masses. Typical carcinoid tumors are low-grade malignancies with no necrosis and fewer than 2 mitoses per 2 mm². Typical carcinoids occur equally in men and women, most commonly around age 50, and are not associated with smoking or any other toxic exposure.⁷ Hilar and mediastinal lymph node metastases occur in 5% to 10% of patients but are not necessarily associated with poor survival.²¹ Atypical carcinoids, which comprise approximately 10% to 20% of all carcinoids, have 2 to 10 mitoses per 2 mm² or a foci of coagulative necrosis. The atypical carcinoids are consistently associated with smoking and 30% to 75% incidence of lymph node metastases.²¹ Patients with pulmonary carcinoid tumors, typical and atypical combined, usually present with obstructive-type symptoms. Carcinoid syndrome symptoms are uncommon with pulmonary carcinoid tumors.

Salivary Gland-Type Tumors

Salivary gland-type tumors, other than ACC, also can arise from the mixed submucosal seromucinous glands and ducts. These tumors are found in the trachea and mainstem bronchi but occur much more frequently in lobar bronchi.⁷ Patients usually present with wheezing or hemoptysis caused by airway tumor growth. Tracheobronchial salivary gland-type tumors are histologically indistinguishable from those arising in the major salivary glands. Benign tumors include mucous gland adenomas, pleomorphic adenomas (also known as benign mixed tumors), oncocytoma, monomorphic adenomas, myoepitheliomas, and epithelial–myoepithelial tumors. Malignant salivary gland-type carcinomas, in addition to ACC described earlier, include low- and high-grade mucoepidermoid carcinomas, acinic cell carcinoma, and salivary gland-type mixed tumors. Other rare salivary gland-type carcinomas that can occur in endobronchial locations are pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, carcinosarcoma, and pulmonary blastoma.

Other Epithelial Neoplasms

Papillomas are benign tracheobronchial epithelial tumors composed of connective tissue with an overlying epithelial surface. Tracheobronchial papillomas generally have an exophytic growth pattern, and their appearance, endoscopically and grossly, resembles a sessile cauliflower-like mass occupying the airway lumen.²² Papillomas are subclassified as squamous cell, glandular, or mixed depending on the type of epithelial lining contained in the tumor.⁷ Squamous cell papillomas, by far the most common type, are associated with human papillomavirus types 6 and 11 and can be either solitary or multiple (squamous papillomatosis).^22,23 The epithelium in these tumors can become dysplastic and progress to carcinoma.

Endobronchial Carcinomas

Although most pulmonary adenocarcinomas are peripheral and involve the larger airways secondarily, endobronchial adenocarcinomas that are histologically distinct from the salivary gland-type tumors do exist.²⁴ These polypoid lesions have a similar prognosis to the more common peripheral adenocarcinomas.⁷ Similarly, one can encounter endobronchial small cell, combined small cell, large cell, and large cell neuroendocrine carcinomas. Combined small cell carcinoma is defined as a small cell carcinoma with an additional component of any nonsmall cell carcinoma histologic type. Large cell carcinoma lacks squamous or glandular differentiation and small cell carcinoma cytologic features; large cell neuroendocrine carcinoma is a variant of large cell carcinoma with neuroendocrine differentiation.

Soft Tissue Neoplasms

The fibroconnective tissues of the trachea and bronchi, which include cartilage, smooth muscle cells, fibroblasts, adipocytes, nerves, lymphatics, and blood vessels, all can give rise to a variety of benign and malignant soft tissue tumors. These tumors are rarer than primary epithelial malignancies of the airway. Hamartoma, the most common benign lung tumor, is a mesenchymal neoplasm that contains adipose tissue, fibrous tissue, and cartilage. These tumors occur mostly in the lung parenchyma, although approximately 10% present in an endobronchial location.⁷ Chondromas and chondrosarcomas arise in the cartilaginous rings of the large bronchi or trachea. Glomus tumors are lesions with smooth muscle features that arise from the posterior membranous trachea. Granular cell tumors are polypoid endobronchial lesions that can invade peribronchial structures.

Vascular tumors such as hemangiomas, hemangioendotheliomas, angiosarcomas, and Kaposi’s sarcoma occur rarely. Similarly, primary pulmonary leiomyomas, leiomyosarcomas, rhabdomyosarcomas, lipomas, liposarcomas, and osteosarcomas are rare tumors that have been found endobronchially. Other sarcomas, such as fibrosarcoma, hemangiopericytoma, malignant fibrous histiocytoma, and synovial sarcoma, have been reported but occur primarily in the lung periphery.⁷ Nerve sheath tumors such as neurofibroma, schwannoma, and neurogenic sarcoma also can occur endotracheally, although these lesions are found far more often in the posterior mediastinum.⁷

Miscellaneous Tumors

Inflammatory pseudotumor and inflammatory myofibroblastic tumors are lesions composed of a spectrum of fibroblastic or myofibroblastic proliferations with a varying infiltrate of inflammatory cells that can occur as endobronchial and endotracheal masses as well as in the lung parenchyma.⁷ The airways also can be involved with lymphoma, either from disseminated disease from a nodal lymphoma or from a primary pulmonary lymphoma arising in bronchial-associated lymphoid tissue. Melanoma, whether in the form of metastatic disease or much more uncommonly a primary pulmonary melanoma, can occur in a similar manner. Thyroid and laryngeal carcinomas can involve the upper trachea by direct extension. Tracheal and mainstem bronchi invasion also can result from metastasis from other primary malignancies, including primary pulmonary adenocarcinomas, malignant mesothelioma, and breast, colon, and renal cell adenocarcinomas.

Patients with upper airway neoplasms typically present with slowly progressive respiratory symptoms such as dyspnea, cough, hemoptysis, wheezing, stridor, excessive secretions, and recurrent pneumonia (Table 60-2).^7,10,11,14 The rate of progression of symptoms tends to be slower with benign tumors and ACC and more rapid with bronchogenic cancers. Because tracheal neoplasms tend to be slow growing, symptoms owing to upper airway obstruction, irritation, or ulceration can continue for months or even years. Acute life-threatening airway emergencies secondary to near-complete airway occlusion are uncommon but can occur. Symptoms related to involvement of adjacent structures, such as hoarseness and dysphagia, are generally less frequent but also can occur. The peak incidence range of the more common upper airway neoplasms is between the ages of 40 and 60 years. Tumors other than SCC and ACC have a scattered age distribution but tend to occur more commonly in young adults.⁵