Chemodectoma

Primary neoplastic disease of the trachea is a rare but important condition to consider in the differential diagnosis of obstructive airway disease. The correct diagnosis is seldom made initially, and a long delay in diagnosis is common for both benign and malignant lesions. The delay in diagnosis of probably due to the lack of early symptoms and signs.

Primary tracheal tumors account for less than 0.1 percent of all malignant neoplasms.[1] Tumors of the larynx and lungs have been reported to occur 75 and 180 times more often, respectively, than malignant lesions of the trachea, and bronchial tumors have been reported to occur 100 times more often than tumors of the trachea. The relative immunity of the trachea, compared with the larynx and bronchi, is probably related to the decreased contact of the tracheal mucosa to carcinogens. In addition, less mucus is trapped in this area because of the cough reflex and the ciliated epithelium of the trachea.

Primary tracheal neoplasms occur with equal frequency in men and women, most often in those 30 to 50 years of age.[2,3] In adults, the lower one-third of the trachea is usually involved.[4] Most tracheal neoplasms arise from the posterolateral wall of the trachea near the junction of the rigid cartilaginous and soft membranous parts of the trachea; at this site the mucous glands are most prominent.[1]

Primary neoplasms may be classified as epithelial, mesenchymal or lymphoid tumors; more than 20 types of tracheal neoplasms have been described. It is important to bear in mind, however, that even "common" tracheal neoplasms are relatively rare and that the presentation, behavior and treatment of benign tracheal neoplasms are independent of the specific histology. In addition, benign lesions cannot typically be distinguished from malignant lesions by presentation, special clinical studies or gross appearance.

Benign Neoplasms

Most benign neoplasms of the trachea (approximately 90 percent) occur in children. The most common lesions are hemangiomas, squamous papillomas and fibromas.[2,3] The lack of many large studies of these lesions makes it difficult to determine their exact incidence. Benign neoplasms can be classified according to their cell of origin: neural (carcinoid; benign clear cell, neurofibroma, myoblastoma), epithelial (pappiloma), mesenchymal (chondroma, lipoma, fibroma, fibrous histiocytoma), and epithelial and mesenchymal (hamartoma).

Other nonneoplastic conditions to be considered in the differential diagnosis of benign tracheal neoplasm include the tracheopathia osteoplastica, intratracheal goiter, rhinoscleroma, Wegener's granulomatosis and amyloidosis.[3,5]

Hamartomas are relatively common in the lungs but are rare in the tracheobronchial tree. All bronchial elements may occur within a hamartoma, including various combinations of cartilage, fatty tissue and epithelium. Ciliated epithelium may line clefts within a tumor, and cystic spaces may be present. Sometimes the lesions contain only undifferentiated mesenchyma.

The average age of patients with tracheal hamartomas at diagnosis is 55 years; most of these lesions occur in 50- to 70-year-old persons. In one series, tracheal hamartomas were reported to be the second most common benign neoplasm.[6] They are considered by some as not truly neoplastic but simply residual embryonic cells within the tracheal wall.

Malignant Neoplasms

Squamous cell carcinoma is by far the most common malignant primary tracheal neoplasm representing approximately 50 percent of all malignant tracheal lesions. Most cases of squamous cell carcinoma in the trachea occur in smokers over 40 years of age, a group that is also vulnerable to similar lesions in the larynx and bronchi.[2]

The term tracheal or bronchial "adenoma" was frequently used in the past to designate a group of tumors that, by localization, growth rate and malignancy, are distinct from bronchogenic carcinomas. The types of tumors considered to be adenomas included carcinoids, cylindromas, mucoepidermoid carcinoma and the rare mucous-gland cystadenoma. Although these tracheal lesions were once considered benign, it is now widely accepted that they are malignant, but have a slower rate of growth and metastatic spread than bronchogenic carcinoma.[7]

Carcinoid tumors represent approximately 85 percent of adenomas of the tracheobronchial tree. Adenoid cystic carcinoma is the most frequent adenoma of the trachea. It represents approximately 30 to 40 percent of all primary tracheal tumors, second only to squamous cell carcinoma.[1,8] Tracheal carcinoids are rare.[2] Carcinoid tumors tend to occur in a slightly younger age group than the other so-called adenomas-adenoid cystic carcinoma and mucoepidermoid carcinoma.[7]

Adenoid cystic carcinoma (or cylindroma) is the second most common malignancy and also the second most common primary tracheal neoplasm. Adenoid cystic carcinoma reportedly accounts for up to one-third of all tracheal malignancies.

Adenoid cystic carcinomas have the same histology as salivary gland neoplasms. They are well known for their insidious nature and their tendency toward perineural cystic carcinomas tend to invade the tracheal wall and adjoining structures, extending submucosally and microscopically for long distances. The course of the disease in patients with this tumor is often relatively benign and protracted, with late metastases.[3,9] Adenoid cystic carcinoma recurs locally in about 50 percent of cases, with metastases to the lungs, brain, lymph nodes, liver, bone and skin in 50 percent.[1] Metastatic disease is rare in primary tracheal malignancies, because patients usually die at an early stage from asphyxiation or other complications. Other rare tracheal neoplasms include adenocarcinoma, leiomyosarcoma, fibrosarcoma, angiosarcoma, lymphoma, oat cell carcinoma, solitary plasmacytoma, hemangioendothelioma car chemodectoma.[3]

Symptoms, Signs and Laboratory Findings

The most frequent symptoms of tracheal neoplasm, related to airway obstruction, are cough, wheezing, dyspnea and recurrent pneumonia.[7,8,10,11] The "tracheal syndrome," described as breahtlessness, wheezing, stridor, hemoptysis and voice change, is present in up to 85 percent of patients with primary tracheal neoplasm.[2] Hoarseness and noisy respiration may predominate in patients with lesions located in the upper one-third of the trachea; partial or complete airway obstruction is most common in patients with lesions in the lower one-third of the trachea.[10] The timber or quality of the patient's voice may change because of the decreased velocity of the air stream passing through the larynx.

Almost all reports of primary tracheal neoplasms include the presence of a wheeze. It is important to bear in mind the clinical maxim: "All that wheezes is not asthma."[2,5] Wheezing that is associated with tracheal neoplasms is typically described as predominantly inspiratory, compared with the expiratory wheezing of asthma.[2] Inspiratory symptoms are most frequent when the lesion is at or near the carina, presumably secondary to descent of the tumor with obstruction of the bronchi during inspiration, with displacement away from the bronchial orifice during expiration.

Orthopnea and paroxysmal dyspnea also occur frequently in patients with tracheal neoplasm. These symptoms may be secondary to the change in position of the tumor as the patient changes body postures, as well as the accumulation of secretions within the trachea during sleep.[4] The trachea may become obstructed by the "ball-valve" mechanism during inspiration, resulting stridor, or by the "check-valve" mechanism during expiration, resulting in hyperinflation and wheezing.[12]

Findings on physical examination that are suggestive of primary tracheal neoplasm include a protacted stenosal murmur. This murmur may be heard as the stethoscope is moved from the larynx to the midsternum in patients who have a narrowed tracheal lumen. If the tumor is in the region of the carina, the examination may occasionally reveal signs of bronchial obstruction, such as decreased breath sounds over one lung.[2]

Pulmonary function testing that shows a linear relationship between volume and time on spirometry, flat-topped expiratory flow-volume loop and a low peak flow relative to forced expiratory volume in one second may suggest the presence of an obstructive tracheal lesion.[13] Sputum may be sent for cytologic examination, but tumor cells are rarely found. Hemoptysis may be present in one-half of cases; profuse bleeding is uncommon.[2] Pain weight loss and malaise are uncommon symptoms of primary tracheal neoplasms, malignant or benign.

Diagnosis

The diagnosis of primary tracheal neoplasm is typically delayed for some time after the onset of symptoms, in both benign and malignant neoplasms. The average delay has been reported to be approximately eight months for malignant lesions and 25 months for benign neoplasms. Some benign lesions have a reported diagnostic delay of up to 16 years.[2] In one study,[8] the authors commented that "the inclusion of tracheal tumors in the differential diagnosis of adult onset dyspnea and wheezing is even more uncommon than the tumors themselves."

The onset of symptoms is usually insidious and, because of the large functional reserve of the adult trachea, the lumen is usually at least 75 percent occluded before symptoms are significant. Generally, the patient makes a good functional adaptation to progressive tracheal narrowing,[3,8,10,11,14] Almost all patients with primary tracheal neoplasms have been treated at some point in the course of the disease for chronic bronchitis or asthma. These disorders are the major diagnostic pitfalls.

It may be clinically difficult to determine if an obstruction is in the upper or lower portion of the respiratory tract. The diagnosis may be delayed if the clinician relies on physical signs and lung function tests alone. Therefore, in a patient with suspected asthma, failure of treatment over a reasonable period of time is an indication for radiographic definition of the central airways. Endoscopy is indicated if the clinical clues listed below suggest the presence of a tracheal tumor. Even if the chest radiograph appears normal, tracheal neoplasm should be considered in all patients with a history of dyspnea, cough and stridor.[15]

The following clues point to the correct diagnosis of tracheal neoplasm: (1) recent onset of asthmatic wheezing, especially in patients older than 40 years of age; (2) wheezing that is more pronounced during inspiration; (3) paroxysmal wheezing that is relieved by, or precipitated by, a change in position; (4) lack of positive response to antiasthmatic therapy; (5) hemoptysis associated with asthmatic wheezing, and (6) orthopnea or paroxysmal nocturnal dyspnea without significant cardiovascular disease. Regardless of the patient's age, an obstructing lesion of the trachea should be considered if wheezing is relieved by or precipitated by a change in position.[4]

ENDOSCOPY AND RADIOLOGY

The diagnosis of a primary tracheal neoplasm is usually made on the basis of endoscopic or radiologic findings. Bronchoscopy is the most definitive diagnostic procedure; it allows direct examination of mucosal detail and provides material for cytologic examination. Biopsy, however, may not be possible in chondroid lesions or in abundantly vascular tumors such as hemangiomas. However, since bronchoscopy is also invasive, it is frequently preceded by other studies.[12]

Radiologic studies include adequately penetrated views of the chest (lateral and oblique), conventional tomographic scanning and, occasionally, lateral neck views, esophagography and fluoroscopy. The tumor is frequently overlooked on standard posteroanterior and lateral views of the chest, since conventional chest films do not always clearly show the tracheal air column. Better tracheal resolution can sometimes be attained by using higher voltage techniques. Xeroradiography was recommended in the past, but this technique is no longer available.[5]

Neoplasms are sometimes readily visible on plain film, particularly on the lateral view, as a disturbance in the tracheal air column[16] (Figure 1). Lesions at the level of T1 will not, however, be visible on a conventional lateral view of the chest. At this level, oblique films are required to avoid the shadow caused by the shoulder girdle.[10] Fluoroscopy may reveal obstructive prolonged expiration. Rarely, mediastinal shift or paralysis of the vocal cords will be seen.[16] Inspiratory and expiratory films have been used to demonstrate the presence of air trapping.[1]

Radiologically, benign tracheal neoplasms appear as well-circumscribed, occasionally lobulated masses, generally less than 2 cm in diameter. They may be broad-based or attached to a pedicle arising from the tracheal wall. Benign lesions are intraluminal and do not extend beyond the tracheal wall. If calcification is visualized, the differential diagnosis is limited to hamartona, chondroma, chondrosarcoma or chondroblastoma.[2,11] If multiple lesions are seen, squamous cell papilloma or tracheopathia osteoplastica should be considered.[3]

The classic description of malignant neoplasms includes an irregular margin with evidence of local extension; these lesions are also typically larger than benign neoplasms.[16] Extension into the mediastinum is common, as is associated thickening of the tracheal wall. Ulceration occurs frequently in squamous cell carcinoma.[3] Malignant lesions may simulate benign ones; no specific radiologic findings reliably differentiate benign from malignant neoplasms.

The evaluation of primary tracheal neoplasms should be carried out with the following goals: (1) determining the local extent of disease; (2) identifying the presence of distal involvement; (3) establishing the histologic diagnosis and (4) determining the extent of the rumor invasion. In the past, conventional tomography was used to evaluate these factors (Figure 2). However, this modality has recently been replaced by computed tomographic (CT) scanning (Figure 3).

CT is extremely useful in excluding or confirming contiguous mediastinal or parenchymal involvement that may be missed by both radiography and conventional tomography.[17-19] Local extent of disease is also better evaluated by CT, and this modality is more sensitive in detecting metastatic disease.[18] CT is also more sensitive in detecting calcification,[5,19] and it is an excellent way to determine the relationship of the lesion to adjacent vascular structures.[20]

CT demonstrates tracheal-wall thickness throughout the circumference, the shape of the exophytic portion of the tumor and the dimensions of the extratracheal portion.[2] Moreover, it is useful in evaluating lung viability distal to an obstructing lesion and may provide a road map for the bronchoscopist.[21] Conventional tomography does, however, still have a role; coronal images are useful in determining the length of the involved trachea. This information may be necessary for the surgeon performing tracheal reconstruction.[2] Direct coronal images can also be obtained with magnetic resonance imaging.[13]

Treatment

Treatment of primary tracheal neoplasms is aimed toward cure or, at least, alleviation of the symptoms of airway obstruction. Treatment modalities include surgery, radiation, laser photocoagulation and cryosurgery. The choice of modality depends on a number of factors, including histology, tumor size, location, growth pattern, patient age and condition, and degree of respiratory disturbance.

Surgery is the primary treatment choice, either an endoscopic procedure or an open procedure.[2] An endoscopic procedure is not suitable for curative therapy, however, even for benign neoplasms, because complete ablation cannot be accomplished without significant risk of injury to the tracheal wall. Therefore, optimal treatment is open resection with end-to-end anastomosis.[22]

Benign tumors are nearly always resectable. Squamous cell carcinoma and

adenoid cystic carcinoma can also be removed surgically if primary airway reconstruction is possible. In patients with adenoid cystic carcinoma, resection may result in excellent long-term palliation and control even when the tumor is incompletely removed. Pulmonary metastasis in adenoid cystic carcinoma is not necessarily a contraindication to primary surgery.

Radiation therapy is useful, particularly in adenoid cystic carcinoma. It is used both postoperatively in extensive neoplasms and as a primary modality in inoperable lesions.[2,9,23] Photocoagulation and cryosurgery may be helpful for tumor debulking and palliation in inoperable cases and preoperatively for large neoplasms.[20]

REFERENCES

[1.] Cleveland RH, Nice CM Jr, Ziskind J. Primary adenoid cystic carcinoma (cylindroma) of the trachea. Radiology 19;122:597-600. [2.] Grillo HC, Eschapasse H, eds. International trends in general thoracic surgery. Vol. 2. Philadelphia: Saunders, 1987:91-106. [3.] Weber AL, Grillo HC. Tracheal tumors. A radiological, clinical, and pathological evaluation of 84 cases. Radiol Clin North Am 1978;16:227-46. [4.] Sanders JS, Carnes VM. Leiomyoma of the trachea. Report of a case, with a note on the diagnosis of partial tracheal obstruction. N Engl J Med 1961;264:277-9. [5.] Slasky BS, Hardesty RL, Wilson S. Tracheal chondrosarcoma with an overview of other tumors of the trachea. J Comput Tomogr 1985; 9:225-31. [6.] Hurt R. Benign tumours of the bronchus and trachea, 1951-1981. Ann R Coll Surg Engl 1984;66:22-6. [7.] Burchart F, Axelsson C. Bronchial adenomas. Thorax 1972;27:442-9. [8.] Parrish RW, Banks J, Fennetry AG. Tracheal obstruction presenting as asthma. Postgrad Med J. 1983;59:775-6. [9.] Grillo HC. Management of tracheal tumors. Am J Surg 1982;143:697-700. [10.] Fleming RJ, Medina Seaman WB. Roentgenographic aspects of tracheal tumors. Radiology 1962;79:628-36. [11.] Weber AL, Shortsleeve M, Goodman M, Montgomery W, Grillo HC. Cartilaginous tumors of the larynx and trachea. Radiol Clin North Am 1978;16:261-7. [12.] Ma CK, Fine G, Lewis J, Lee MW. Benign mixed tumor of the trachea. Cancer 1979;44: 2260-6. [13.] Chen TF, Braidly PC, Shneerson JM, Wells FC. Obstructing tracheal lipoma: management of a rare tumor. Ann Thorac Surg 1990; 49:137-9. [14.] Hurst IJ Jr, Nelson KG. Tracheal hamartoma. Chest 1977;72:661-2. [15.] McGregor CG, Herrick MJ, Hardy I, Higenbottam T. Variable intrathoracic airways obstruction masquerading as asthma. Br Med J [Clin Res] 1983;287:1457-8. [16.] Janower ML, Grillo HC, MacMillan AS Jr, James AE Jr. The radiological appearance of carcinoma of the trachea. Radiology 1970; 96:39-43. [17.] Allen HA, Angell F, Hankins J, Whitley NO. Leiomyoma of the trachea. Am J Roentgenol 1983;141:683-4. [18.] Meredith HC, Valicenti JF. Solitary neurofibroma of the trachea. Br J Radiol 1978;51: 218-9. [19.] Gamsu G, Webb WR. Computed tomography of the trachea and mainstream bronchi. Semin Roentgenol 1983;18:51-60. [20.] Pearlberg JL, Sandler MA, Kvale P, Beute GH, Madrazo BL. Computed-tomographic and conventional linear-tomographic evaluation of tracheobronchial lesions for laser photoresection. Radiology 1985;154:759-62. [21.] Naidich DP, McCauley DI, Siegelman SS. Computed tomography of bronchial adenomas. J Comput Assist Tomogr 1982;6:725-32. [22.] Pollak ER, Naunheim KS, Little AG. Fibromyxoma of the trachea. A review of benign tracheal tumors. Arch Pathol Lab Med 1985; 109:926-9. [23.] Pearson FG, Todd TR, Cooper JD. Experience with primary neoplasms of the trachea and carina. J Thorac Cardiovasc Surg 1984;88: 511-8.

SALVATORE A. DELUCA, M.D., coordinator of this series, is assistant professor of radiology at Harvard Medical School and associate radiologist at Massachusetts General Hospital, Boston.

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