Primary Malignant Tumors of the Trachea A Radiologic and Clinical Study

Wei Li, MD,*$ Nancy A. Ellerbroek, MD,t and Herman I. Libshitz, MD*

Fifty-four cases (55 foci) of primary tracheal malignancies were reviewed retrospectively. Radiologic material was available in 32 cases (33 tracheal foci). The most frequent primary malignant tumor of the trachea was squamous cell carcinoma (54.5'/0), followed by adenoid cystic carcinoma (18%) and adenocarcinoma (9"/0). The radiologic appearance of the tumors could be divided into intraluminal, wall-thickening, and exophytic forms. Wall-thickening and exophytic forms in this study accounted for 62% of the tumors. This indicates that malignant tumors of the trachea tend to extraluminal invasion. Tomography and computed tomography are the most helpful methods of radiologic examination for tracheal tumors. Bronchoscopy and radiologic examination are complementary procedures. The chief advantage of imaging is the demonstration of tracheal wall thickening and extraluminal changes. Hemoptysis, dyspnea, and cough were the most common symptoms. Four cases (7%) in our series presented as thyroid tumors due to direct extension into the thyroid gland. Fifteen of the 54 cases ( Z ~ ' / O ) were associated with other carcinomas of the head and neck and the lung. Cancer 66:894-899,1990,

HE INCIDENCE OF primary tracheal carcinoma is less T than 0.2 per 100,000 people per year. The post- mortem prevalence is about 1 per 15,000 autopsies, and tracheal cancer is responsible for less than 0.1 % of cancer deaths.' This study was undertaken to describe and an- alyze relevant radiologic and clinical features of this un- common malignancy.

Materials and Methods

The medical records of 54 patients with primary ma- lignant tumors of the trachea were reviewed retrospec- tively. The cases were obtained from the records of the Division of Patient Studies and the database of the De- partment of Clinical Radiotherapy, The University of Texas M. D. Anderson Cancer Center, from 1949 to 1988.

From the Departments of *Diagnostic Radiology and ?Clinical Ra- diotherapy, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.

The authors wish to thank Irwin M. Freundlich, MD, for editorial suggestions and Debbie Smith for the preparation of the manuscript. + Current address: Friendship Hospital, Beijing, People's Republic of China.

Address for reprints: Herman 1. Libshitz, MD, Department of Diag- nostic Radiology, M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030.

Accepted for publication February 15, 1990.

Tumors invading the trachea secondarily from adjacent organs were not included. The histologic types of tumor in the 54 cases ( 5 5 foci) are shown in Table 1. There were 30 squamous cell carcinomas (SCC), ten adenoid cystic carcinomas (ACC), and five adenocarcinomas (Ad.C.). Additionally, there were three small cell carcinomas, one large cell carcinoma, one fibrosarcoma, and five undif- ferentiated or unclassified carcinomas.

Fifteen foci were confirmed by operation and the other foci by biopsy at bronchoscopy or autopsy. Of the 54 pa- tients, radiologic material at the time of diagnosis was available in 32 cases (33 foci).

Results

Data on sex and the average age at the time of diagnosis are outlined in Table 2. The age range was 37 to 83 years in males and 25 to 81 years in females.

Of the 54 patients with primary malignant tracheal tu- mors, no records of symptoms were available in six cases. The symptoms of the other 48 cases are outlined in Table 3 . Hemoptysis, dyspnea, and cough were the more com- mon symptoms.

One patient had two primary tracheal tumors. The original malignancy was a small cell carcinoma in the lower third of the trachea. The patient was treated with

8 94

No. 5 PRIMARY MALIGNANT TRACHEA TUMORS * Li et al. 895

Types

see ACC Ad.C Others

Total

-

TABLE 1. Primary Tracheal Malignancies

Single tracheal Multiple primary malignancies malignancies

Involving Different Same

only organs types types Total

11 5 2 12 30 8 2 0 0 10 2 3 0 0 5 9 0 1 0 10

30 10 3 12 55

Trachea adjacent histologic histologic

SCC: squamous cell carcinoma; ACC adenoid cystic carcinoma: Ad.C adenocarcinoma.

an extensive chemotherapy and autologous bone marrow transplantation regimen followed by radiotherapy. A complete remission of the small cell carcinoma was ob- tained. At the completion of radiation therapy, 14 months after initial presentation, a new tumor was discovered in the same area. The second tumor was resected and the surgical specimen revealed a malignant spindle cell neo- plasm compatible with sarcoma. At autopsy, the diagnosis was fibrosarcoma.

Four of the ten cases that directly invaded adjacent organs presented with neck masses and were initially sus- pected to be thyroid tumors. Other adjacent organs di- rectly invaded by tracheal tumors were: esophagus, one; larynx, two; and bronchus, three.

In six cases of single primary tumors, multiple nodules, presumed to be metastases, were found in the lung of the same histologic type as the tracheal tumors. The tracheal lesions preceded the lung lesions. Two of the six cases had various bony metastases.

Twenty-nine cases had chest radiographs. Five were normal, and 12 revealed widening of the mediastinum, because of invasion by tumor or enlarged lymph nodes. Pneumonia and/or atelectasis was seen in three cases. Masses of the lung were seen in five. Tracheal masses could be seen, sometimes poorly defined, in 15 cases (Fig.

TABLE 2. Sex and Average Age of Patients With Primary Tracheal Malignancies

Men Women Total

Age Age Age Tumors No. (yr) No. (yr) No. (yr)

SCC 25 59.4 5 67.0 30 60.6 ACC 5 55.0 5 39.6 10 47.3 Ad.C 3 57.7 2 70.5 5 62.8 Others 3 60.0 6 59.8 9 59.9

TABLE 3. Symptoms Associated With Primary Tracheal Malignancies (n = 48)

Symptoms No. Percent

Hemoptysis Dyspnea cough Hoarseness Dysphagia Weight loss Wheezing Neck mass Stridor Chest pain Cyanosis

21 25 21 16 11 I 1 7 4 4 3 1

56.3 52.1 43.8 33.3 22.9 22.9 14.6 8.3 8.3 6.3 2.1

1). Eleven patients had plain films of the neck. Seven tumors were well demonstrated (Fig. 2). The tumor was not seen in four cases because the tracheal masses was too low. Barium swallow was used in seven cases (Fig. 3). Tracheography was carried out in three cases.

Total 36 58.7 18 57.4 54 58.2 FIG. 1. Frontal chest radiograph shows an exophytic mass of the left side of the trachea causing mediastinal widening. The trachea is displaced and narrowed by the tumor. Squamous cell carcinoma of the trachea was confirmed by biopsy at bronchoscopy.

SCC: squamous cell carcinoma: ACC adenoid cystic carcinoma: Ad.C adenocarcinoma.

896 CANCER September 1 1990 Vol. 66

the thickened part presents either a flat or spindle-shaped mass along the tracheal wall (Fig. 3 ) . The exophytic type (four cases) is characterized radiologically by the tumor appearing to be extratracheal in origin despite its arising in the trachea. In some cases, the extratracheal mass gives rise to mediastinal widening with an abnormal contour, appearing as a paratracheal mass. The trachea is often markedly deviated and narrowed by compression due to the mass (Fig. 1).

Fifteen cases were associated with other malignancies. In three cases the tracheal tumor and the others were of different histologic types (Table 5). Twelve cases had the same histologic type; all were SCC (Table 6). Of the 12 patients with the same histologic type, tracheal tumors were found before the others in two cases, synchronously in two cases, and after at least one of the others in eight cases. In all 15 cases, the tracheal lesions were associated with head and neck tumors (six cases), with cancers of the lung or the bronchus (six cases), or with both (three cases).

FIG. 2. Lateral view of the neck shows a sharply defined, hemispher- ically shaped mass arising from the posterior wall of the upper trachea. This intraluminal mass occluded approximately 75% of the tracheal lu- men. Adenoid cystic carcinoma was confirmed by surgery. The subglottic area of the larynx was involved.

Of 22 cases with conventional tomography, tracheal masses were well demonstrated in 21 cases (Fig. 3 ) and were absent in one. Twelve cases had computed tomog- raphy (CT) at the time of diagnosis. The shape, margin, extent of the tracheal masses, and the relationship between the tumors and the adjacent structures were well identified in 11 cases on CT images (Fig. 4). The tumor was not seen in one.

The radiologic appearance of the tumors could be di- vided into three types: intraluminal, wall-thickening, and exophytic in 29 of 33 foci (Table 4). Four foci were in- determinate because the contour of masses was not clear on the chest films and other studies were not performed. Eleven cases presented as the intraluminal type in which the tumors were intraluminal, hemispheric masses limited in spread to the tracheal wall (Fig. 2). Fourteen cases pre- sented as wall-thickening. In this appearance the wall of the trachea is thickened by infiltration of the tumor, and

Discussion Tumors arising from the trachea are rare, and 50% or

more are malignant in adults.' The most frequent ma- lignant tracheal tumor is SCC, followed by ACC and Ad.C.'-3 Sixty percent occur in men older than age 40.4 ACC develops at a much younger age than SCC, and even has been reported in teen-agers.' Our results are similar (Table 2).

Respiratory obstruction and hemoptysis are the chief clinical manifestations of tracheal tumors'32 and occurred in more than half of our patients. Cough, hoarseness, and dysphagia, symptoms related to involvement of the ad- jacent structures, were less frequent (Table 3). Because of the lack of specific symptoms, and the rarity of the tumor, early diagnosis is unusual.

Thyroid carcinoma commonly involves the tracheal wall and may invade the lumen,6 but it is uncommon for primary tracheal neoplasms to extend into the thyroid gland and present as a thyroid mass.' Four cases (7%) in our series presented this way. Tracheal carcinoma mim- icking a thyroid cyst has also been reported.'

Sarcoma of the trachea is very rare in any age group, but among children it is probably encountered more often than epithelial malignancies. Fibrosarcoma, myosar- coma, rhabdomyosarcoma, leiomyosarcoma, chondro- sarcoma, liposarcoma, carcinosarcoma, angiosarcoma, and Kaposi's sarcoma are In our series, one case of tracheal fibrosarcoma arose after radiation therapy for a small cell carcinoma of the trachea. However, it cannot be called a radiation-induced sarcoma, because of the absence of a latent period following the radiotherapy.I2

The histologic diagnosis of tracheal tumors is usually made at bronchoscopy with biopsy of the trachea. How-

No. 5 PRIMARY MALIGNANT TRACHEA TUMORS - Li et al. 897

FIGS. 3A AND 3B. (A) Lateral tomogram shows a tracheal cancer causing wall thickening. A spindle-shaped mass is seen along the left posterior wall of the lower trachea. The lumen of the trachea is narrowed. (B) Barium swallow depicts the contour of the mass. Poorly differentiated invasive squamous carcinoma was confirmed by biopsy of the trachea at bronchoscopy.

ever, the current series demonstrates that radiologic ex- amination plays a vital role both in discovery and deter- mination of the extent of the neoplasm and in providing a basis for re-examination. The extent of the tumor, the relationship to adjacent organs, and presence of metastatic lymphadenopathy are all important considerations in treatment planning.

Tracheal tumors are not easily discovered by routine chest radiographs. 2,4, 3-1 In our series, tracheal masses could be identified, sometimes with difficulty, in only 52% ( 15/29) of chest radiographs. The lateral view of the chest is particularly important because the thoracic spine and mediastinal structures are superimposed on the trachea in the frontal projection.

Early involvement of the tracheal wall with slight thickening is difficult to assess radiologically particularly when it occurs on the left wall of the trachea near the aortic arch. It is difficult to determine whether the ap-

pearance is thickened tracheal wall or compression by the aortic arch. Identification of an irregular margin of the tracheal mucosa helps in making this distinction.

Radiographs of the neck are useful for demonstrating the tumors arising from the upper third of the trachea because of the contrast between air and tumor tissue (Fig. 2). Barium esophagram examination is helpful in depict- ing the contour of a mass arising from the posterior tra- cheal wall (Fig. 3), as well as identifying invasion of the esophagus. Conventional tomograms demonstrated the tracheal masses in 2 1 of 22 cases (95%) in our series.

Over the past decade, CT has become a very important imaging modality for tracheal tumors. CT demonstrates the relationship to the surrounding structures and provides a cross-sectional view of the trachea.'4316 Spizarny et al. and Shepard el al. and report CT provided incremental information beyond tomography in 70% of cases. When compared to findings at surgery and pathology, the ac-

898 CANCER September 1 1990 Vol. 66

FIGS. 4A AND 4B. A 59-year-old man with two separate synchronous squamous cell carcinomas. (A) A lung window (level: -700; width: 1000) CT image demonstrates an intraluminal mass on the left wall of the trachea. The mass was not visible on the same image at soft tissue window. (B) A PA chest radiograph shows left lower lobe collapse secondary to a separate malignancy in the left lower bronchus.

curacy of CT equalled or exceeded tomography. However, CT may underestimate the longitudinal extention of the lesion because of partial volume averaging and the ten- dency of the tumor to grow submu~osa l ly . ' ~~ '~ CT is also a poor predictor of mediastinal organ invasion.16 In 92% (1 1/ 12) of cases, the tumor masses were well demon- strated. However, sometimes small tumors in the lumen of the trachea are visible only with CT images at lung window settings and could be missed at soft tissue window settings (Fig. 4).

Malignant tumors of the trachea may occur before, si- multaneously, or after another malignancy of the respi- ratory or upper digestive tract.8,'8 The problem when sep- arate foci of malignancy are found is to determine whether the new lesion represents a new primary tumor or a me- tastasis from the original malignancy. lt is generally ac-

TABLE 4. Radiologic Appearance of Primary Malignant Tumors

Forms of masses Widening of

Types No. I W E In mediastinum

SCC 19 7 7 3 2 6 ACC 4 2 2 0 0 1 Ad.C 4 0 1 1 2 4 Others 6 2 4 0 0 1

Total 33 1 1 14 4 4 12

SCC. squamous cell carcinoma: ACC adenoid cystic carcinoma: Ad.C: adenocarcinoma; I: intraluminal; W: wall thickening; E: exophytic; In: indeterminate.

cepted that if the tracheal lesion antedates the other tumors or the tracheal lesion has a different histopathologic type than the other tumors, it represents an independent pri- mary m a l i g n a n ~ y . ' ~ - ~ ~ Multiple lesions of the lung seen on chest radiographs are usually metastatic. l9 However, if the tracheal lesion is of the same histopathologic type as a prior or synchronous malignancy it may be difficult to definitely determine whether it is a new primary tumor or a metastatic deposit.20 Although there is not definite proof, we believe these ten cases of tracheal lesions were most likely new or separate primary malignancies (Tables 5 and 6). Metastases to the tracheal are extremely

There is a greater likelihood of developing multiple pri- mary carcinomas in the same system than in unrelated

rare. 1,19,23,24

TABLE 5. Primary Tracheal Malignancies Associated With Multiple Tumors (Different Histologic Types)

Patient Age Histologic type no. Sex (yr) Organ involved (yr)

1 F 68 Thyroid (1954) Trachea (1966)

2 M 66 Waldeyer's ring (1978) Prostate ( I 980) Skin (1981) Trachea ( 198 1 )

3 F 68 Lung(1981) Trachea ( I 986)

Papillary Ad.C SCC Lymphoma Ad.C SCC Undiff. Ca. Ad.C SCC

Ad.C: adenocarcinoma; SCC: squamous cell carcinoma; Ca.: carci- noma.

No. 5 PRIMARY MALIGNANT TRACHEA TUMORS - Li el al. 899 TABLE 6. Primary Tracheal Malignancies Associated With Multiple Malignancies of the Same Histologic Type

SCC Patient Age

No. Sex (YT)* First/yr Second/yr Third/yr

1 M 56 Trachea/ 1964 Larynx/] 968 2 M 65 Trachea/l981 Lung/S mo later 3 M 59 Bronchus/l983 Trachea/ 1 9 8 3 4 M 65 Larynx/ 1984 Tracheal 1984 5 M 48 Larynx/ 1956 Trachea/1959 6 M 67 External auditory canal/ 1962 Tracheal1970 Lung/ 197 1 7 M 64 Larynx/l964 Trachea/ 197 1 Lung/ 197 I 8 M 53 Tongue/ 1972 Tracheal1974 Lung/ 1974 9 M 1 5 R. lung/ I977 L. lung/l979

10 M 47 Lung/ 1970 Trachea/1977 I 1 M 70 Lung/ 1974 Tracheal 1978 12 M 72 Tongue/ 1973 Tracheai1985

Trachea/1983

SCC: squamous cell carcinoma.

tissues.25 The head and neck and the lung are very often involved by multiple primary cancers, and patients with one tumor are more likely to develop a second one.20,22,25,26 The increased risk is estimated to be as much as 1 1-fold."

In this series, 28% (1 5/54) of primary tracheal malig- nancies were associated with multiple tumors. This is higher than the 18.5% reported by Weber and Grillo,' but similar to 29.3% reported by Hajdu et a/." Vrabec points out that the physician engaged in the care of patients with cancer of the head and neck area should be prepared not only to treat the first malignancy but also to make a thor- ough search for simultaneously occumng malignancies and to maintain a constant vigilance for subsequent ma- lignancies.25 A patient with two primary lesions can be considered potentially curable, while a tumor believed to be a metastatic deposit suggests systemic disease. l 9 There- fore, recognition of the association of primary tracheal tumors with multiple malignancies is clinically important. Each of the separate primary malignancies must be treated aggressively as if each existed alone.

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