Chemodectoma

We conducted a review of all the bronchoscopies performed at our institutions for benign tumors from 1980 to 1991 to determine the endoscopic characteristics of these lesions. We reviewed the charts, the endoscopic characteristics from our video records, and finally the pathologic findings of these cases. We tried to identify the effectiveness of laser resections in each group. Of a total of 3,937 patients, 185 (4.7%) were benign tumors. On these patients, 317 procedures were carried out. There were 3 myoblastomas, 53 papillomas, 1 adenoma, 8 chondromas, 4 fibromas, 45 hamartomas, 15 hamartochondromas, 6 lipomas, 19 angiomas, 5 leiomyomas, 4 schwannomas, 1 neurofibroma, and 21 amyloidomas. Results of laser resection were "very good" in 115 (62%) and "good" in 70 (38%). Complications were minimal: two mediastinal emphysemas, one pneumothorax, and one anesthesia-related cardiac arrest leading to the single death in this series. In general, benign tumors of the proximal endobronchial tree responded well to laser resection when their endoscopic appearance is recognized and prognosis known. Even when recurrent, repeated procedures can be performed easily with good results. This series is probably the largest in the world's literature about endoscopic recognition and the role of laser resection in patients presenting with benign endobronchial tumors. (CHEST 1995;107:1744-51)

Most tumors of the tracheobronchial tree are malignant in nature. Benign tumors are quite rare (approximately 1.9% of all lung tumors). There is considerable confusion regarding the nomenclature, classification, and most significantly, the approach to therapy. Most published data are case reports or experiences from very small series.[1-10]

The Laser Center of the Sainte Marguerite Hospital in Marseille, France, and the Center for Respiratory Endoscopy and Laser Therapy at the Spedali Civili in Brescia, Italy, are tertiary referral centers for patients with endobronchial lesions that may require laser therapy. The combined experience of these centers in the last 10 years is presented herewith. Much controversey exists regarding the classification of endobronchial tumors. Most workers follow modifications of Liebow's original classification. For example Arrigoni et al[11] present 130 such lesions treated by surgery from a 10-year surgical-pathologic review. They mention that "endobronchial tumor involvement was so unusual (6%) that endoscopic examination was precluded." Further they included such entities as "pseudotumors" (see below).

We restrict our classification to the lesions that may be encountered by an endoscopist, which thus are strictly endobronchial. This would be at variation with a classification based on tumors found at surgery or in pathologic specimens.

Materials and Methods

Over the past decade (1980 to 1991), 1,550 patients were referred for endoscopy and laser resection to the Laser Center at Marseille, France, and 2,387 to Spedali Civili, Brescia, Italy (total of 3,937 malignant and benign lung tumors). Of these, 185 were diagnosed (by the Department of Pathology, either before or after referral) to be benign tumors as defined above. Cases referred for thoracic resection first, either for a known benign tumor (bronchotomy, etc) or for a tumor believed preoperatively to be malignant, were not included in our series. We classified these benign tumors as illustrated in Table 1.[12-27] Three hundred seventeen procedures were carried out on these patients to treat their endobronchial lesions. We conducted a review of all the bronchoscopy records, specifically elucidating endoscopic characteristics and the effectiveness of laser resections for each group of lesions. Photographs and video records were also reviewed. Pathologic material typical of these lesions were reviewed.

All patients underwent routine prebronchoscopy investigation, including chest radiography. Computed tomography (CT) of the chest was performed when necessary, but was not a prerequisite. After an informed consent, patients were reexamined in the bronchoscopy/laser suite. The rigid bronchoscope under general anesthesia (propofol/diazepam/phenoperidine), unless contraindicated, was the preferred instrument of choice at both centers. We prefer a rigid bronchoscope. When lesions were too distal in the airway, beyond the reach of the rigid scope, the flexible scope was used through the rigid scope. The extent of endobronchial spread, invasion of the wall of the airway, and recurrence potential were noted.

Laser Resection

After mechanical resection of the endoluminal mass, laser vaporization of the tumor stump was carried out as described earlier[28-33] with the Nd-YAG laser at 15 to 50 W in 1-s bursts. The surrounding wall was treated with low power and long exposure times (20 to 30 Watts; 4- to 6-s pulse duration; 1.000 to 3,000 J) in order to coagulate the wall in depth and to prevent recurrence. Constant suctioning was carried out under direct vision Airway patency and oxygenation were maintained at all times. When satisfactory laser resection was achieved, the bronchoscopy was then removed and the patient sent to the recovery roc m breathing spontaneously, to be discharged back to the ward or to home. Most often a repeated bronchoscopy for surveillance purposes was performed (without laser use) in about 4 to 6 weeks.

Results

Clinical Findings

Table 2 lists the clinical characteristics of the benign airway tumors encountered at bronchoscopy classified by their incidence, age and gender distribution of patients, location, and the number of laser procedures performed. Papillomas and hamartomas accounted for the majority, as has been the experience with other authors.[11] The ages ranged from 6 to 86 years (mean, 54.4 years). The peak incidence was in the sixth decade. There were 143 male (77%) and 42 female (23%) patients.

[TABULAR DATA 2 OMITTED]

The location of these tumors is as follows: 54 were located in the trachea (29%); 1 in the right main bronchus (0.5%); 8 in the bronchus intermedius (4.3%); 14 in the right upper lobe bronchus (7.6%); 8 in the right middle lobe bronchus (4.3%); 10 in the right lower lobe bronchus (5.4%); 23 in the left main bronchus (12.5%); 16 in the left upper lobe bronchus (8.7%); 14 in the left lower lobe bronchus (7.6%); and 37 at multiple sites (20%).

Because these were slow-growing lesions, they rarely caused symptoms when small. When symptomatic, it was because of consequences of airway obstruction (cough, dyspnea, postobstructive pneumonia, and localized wheeze) or vague chest pain, cough, and very rarely hemoptysis. They were often diagnosed fortuitously at bronchoscopy done for unrelated conditions or at pathologic study done essentially to "rule out malignancy." The signs, symptoms, and radiologic features could not be used to distinguish one from the other or between benign and malignant lesions. "Popcorn" calcification was often seen in pulmonary hamartomas on radiography or CT[34] but was difficult to visualize when the tumors were purely endobronchial. Similarly, when endobronchial, these tumors rarely shed cells into the tracheobronchial tree to permit cytologic diagnosis from the sputum.

Bronchoscopic Features of These Lesions and Role of Laser Resection

The bronchoscopic appearance of these lesions and their response to laser photo resection is as described in Table 3.

[TABULAR DATA 3 OMITTED]

1. Myoblastomas: These are also called Abrikossoff tumors after Abrikossoff[35] who first described five such cases with tongue involvement in 1926. They are usually found in the tongue and skin, but are rare in the tracheobronchial tree. They are believed to arise from embryonal rest cells in muscle or from perineural fibroblasts.[36,37] They are irregular-appearing lesions with a portion burrowing into the walls of major airways. Sometimes they may appear as raised plaques. These lesions can be resected by laser but because of their exobronchial spread, incomplete excision is frequent and repeated sessions may be needed. This was the case in one of our two patients. Though benign, squamous metaplasia and local invasion are frequent, simulating a malignant tumor of the bronchus. Myoblastomas have been reported to be multicentric.[36]

2A. Papillomas: These lesions may be localized or extensive (Fig 1).[38] They have an unmistakable fimbriated or "salmon egg" appearance. They are strictly endoluminal and rarely may obstruct the airway. They are believed to spread by contagion or "seeding." Hence, laryngeal papillomas can spread distally in airways or at tracheostomy sites. If they spread into the pulmonary parenchyma, they can produce nodules that cavitate.

The localized form is easily vaporized by laser discharges. Care must be taken to destroy them completely, lasing the entire base from which they originate; this may produce minimal but controllable hemorrhage.

The extensive form of the tumor has a wide base that may show submucosal infiltration. They are difficult to remove completely. Consequently, recurrence is the rule, necessitating repeated sessions of laser resection. Eleven of our 16 patients needed more than one laser session, some as many as 9 up to the time of writing of this article. They have a tendency to undergo malignant transformation if they are present for a long time or if they have undergone irradiation.[12-15]

Papillomas exhibiting human papilloma virus 16 or 18 positivity are at high risk for carcinomatous transformation (squamous cell carcinoma).[15] Hence close follow-up with surveillance bronchoscopies is often needed. We know of no therapy available at present that "cures" these lesions, though interferon and phototherapy using hematoporphyrin derivatives are being tried (personal communication, A.C. Mehta, Cleveland Clinic Foundation, March, 1993). Thoracotomy with resection can still result in recurrence. Recently, we have tried endoluminal stenting after laser resection with good results. The stent appears to delay recurrence and hence maintain airway patency.

2B. Adenomas: As defined above, adenomas are rare mucous gland tumors that are truly benign.[24,25,39] They have a smooth surface and a rounded appearance. The surface may be ulcerated. They are easily resected by laser bronchoscopy. The tumors do not spread beyond the confines of the bronchial wall or metastasize.

3A-D. Chondromas, Fibromas, Hamartomas, Hamartochondromas: These lesions are believed to represent a histologic spectrum of benign mesenchymal neoplasms.[40-41] On microscopy and ultrastructural examination,[42] all demonstrate a characteristic stellate undifferentiated mesenchymal cell appearance along with other elements. Morphologically, they all behave in a similar manner. They are usually pale, whitish yellow in appearance, and what may be called "smooth" or "hard" (Fig 2). The "smooth" variety are easily removed completely with forceps (if small) or with minimal bursts of laser discharges. The "hard" variety, however, have a gritty consistency owing to calcification. Because of this, they are difficult to remove completely with laser discharges. However, even if small portions are left in the airway because of incomplete removal, they do not recur and may not pose any clinically significant problems in the future.

Hamartomas comprised 45 of our 185 cases (24.3%) of all benign lung tumors. They are considered to be the most frequent of "true" benign airway tumors if papillomas are excluded. They are believed to be developmental in origin, arising when an area of the embryonal bronchial tree becomes "inverted" and detached during fetal life. These tumors hence may be multiple when peripherally located. They are composed of a mixture of bronchial components. Cartilaginous elements predominate; a few may have predominantly adipose tissue or bone and bone marrow elements and others myxoid connective tissue. Epithelium lining the clefts may be columnar, ciliated, or cuboidal. They often possess a spiculated pattern of calcification giving rise to the characteristic "popcorn" pattern on radiography or CT.[34]

Hamartomas can have an elastic consistency when pulled by forceps, hence may stretch for a considerable length within the airway, retracting when released. They may be resected by laser discharges but components frequently may be left behind. They do not grow or recur. Most of our cases (12/14) needed only one laser resection. They may be multiple when peripherally located, through none of our cases were multiple.

There have been reports of hamartomas being associated with unrelated pulmonary tumors, both benign and malignant. Peripheral hamartomas can be associated with congenital malformations as in the "Cowden's syndrome" (goiter, lipomas, gastrointestinal polyps, pectus excavatum and other bony abnormalities, hernias, and increased incidence of malignant tumors). This is apparently distinct from the so-called "pulmonary hamartoma syndrome" (inguinal hernias, congenital bony abnormalities, cardiovascular abnormalities, deafness, other benign and malignant tumors).[43-44] There is one isolated report of malignant change in a hamartoma[45] and one concurrent occurrence of bronchioloalveolar carcinoma.[46] None of our cases were associated with congenital abnormalities or concurrent tumors, nor have we noticed any malignant transformation in our 14 cases.

3E. Lipomas: Though lipomas are the most common benign neoplasms overall, occurrence within the thorax is uncommon. They were first described by Rokitansky[47] in 1854 as an autopsy finding, appearing as yellowish fatty submucosal lesions with a lobulated appearance. Pedunculation may occur in some lesions. They may occasionally have blood vessels visible on their surface, especially if long standing and with infection distal to the obstruction. Hence hemoptysis may not be the presenting symptom.[48-50] A CT scan density coefficient similar to fat may be diagnostic of lipomas. Almost all lipomas are completely endoluminal and hence are totally removable by laser discharges. Recurrence is unusual, hence, a single laser bronchoscopy session may be curative (two thirds of our cases). Rarely, the lesions may be "hour-glass" in shape with an intrabronchial portion and an extrabronchial extension. This is due to their origin from fat between cartilages rather than from submucosal fat. They have a unique and characteristic "cooked-fat odor" when vaporized with laser. The pliable capsule may resist "biting" by the biopsy forceps at bronchoscopy. Hence endobronchial biopsy specimens are frequently nondiagnostic.

3F. Angionmas: These tumors can be localized or extensive. They are reddish lesions that may be patchy in distribution. There may be a submucosally infiltrative portion. They are notorious for their tendency to bleed during laser discharges, hence care must be taken to achieve maximum coagulation at low power with minimal penetration. Complete cure is common with this technique, and recurrence is unusual.

3G. Leiomyomas: Leiomyomas (Fig 3) occur in young patients, usually in the second to fourth decade (in contrast to leiomyosarcomas that occur in the fifth decade.[17,18,20,21] These lesions cannot be distinguished solely by their endoscopic appearance. Histologically, they are composed of long interlacing fascicles of spindle cells with abundant elongated eosinophilic cytoplasm. Hypocellularity is often associated with stromal hyalinization and marked decrease of the vascular framework. Nuclei are oval, indented with delicate chromatin with small inconspicuous nucleoli, and devoid of atypical mitoses. They may be difficult to differentiate from fibromas, neurofribromas, and schwannomas by light microscopy alone. Immunoperoxidase staining for vimentin, actin, and S100 protein are positive in leiomyomas. Sometimes solitary smooth muscle metastases may also appear like leiomyomas though the latter are usually smaller (1 to 2.5 cm in size).

3H,I. Schwannomas and Neurofibromas: These lesions (Fig 4) may be single or multiple, the latter occurring in young patients with neurofibromatosis.(19) Unger et al23 described 30 cases of primary neurogenic tumors in patients without neurofibromatosis (von Recklinghausen's disease). These lesions too cannot be distinguished by their endoscopic appearance alone. Histologically, they have a large base. They are polypoid, w ith fascicles of spindle cells and palisading nuclei. There may be hyalinization of vascular walls, hemorrhage, and focal pseudocystic degeneration. Some areas may also have atypical, giant cells.

4. Amyloidomas: Amyloidomas (Fig 5) are characteristically yellowish and lobulated. The limited form can be completely vaporized. The extensive form has a tendency to recur, as in four of our six cases. One patient needed 8 sessions, and one needed 16; both have shown no further recurrence with endobronchial stenting. Colchicine therapv has been tried with limited success in these lesions.

Response to Laser Therapy

We classified results as "very good" if the tumor could be completelv removed at the first session of laser bronchoscopy. If the tumor could be only partially removed but required repeated sessions with no complications, the results were classified as "good." This occurred when the implanting base w as bevond the range of the laser. In patients being treated for cure, one of us (S.C.) intentionally performs two treatments: the first to resect the endoluminal mass, and the second to treat the wall in-depth. The results of these patients are also classified as "very good." "Poor" results signified that the lesion could not be removed with laser bronchoscopy.

One hundred fifteen (62%) had very good results and 70 (38%) had good results. There were two small mediastinal emphysemas in two patients treated for a fibroma of B4 of middle lobe and a liporna of B7. The patients were asymtomatic and the mediastinal emphysemas were detected only by routint postprocedural x-rays. There was one pneumothorax in a patient with a hamartoma of left B6. All resolved spontaneously in a few days. There was cne death from cardiac arrest from general anesthesia. These rcsponses are significantly superior to those obtained for malignant tumors. The incidence of complications with laser photoresection of benign tumors is also insignificant when compared with malignant lesions. Table 3 represents the authors, impression of the appearances of the tumors and the results of laser therapy.

Discussion

Over the past decade, laser resection ha, increasingly been used to treat both benign and malignant endobronchial tumors. When appropriat ly used, laser resection should be considered as the first line of therapy in benign endobronchial tumors. We believe the best indications for laser resection are as follows: (1) strictly endoluminal nature of the tumor; (2) limited extent within the endobronchial tree (within the trachea, mainstem bronchi, bronchus intermedius, and sometimes in the proximal lower lobe bronchi; (3) low probability of recurrencl; (4) patients who are considered to be poor surgical risks; (5) patients who are symptomatic from airway compro mise or may be expected to be so because of the location and extent of the lesion; and (6) recent collapse of lobe/lung if collapse does occur.

If these lesions are asymptomatic and are not likely to cause significant airway obstruction, the "wait and watch" approach may be appropriate, with repeated bronchoscopy at suitable intervals. However, since all tumors (whether benign or malignant) do eventually grovv in size in the airway, and since the treatment can be relatively uncomplicated, we now usually treat with laser all such benign tumors even if they are associated with no symptoms.

If symptomatic or significant obstruction is imminent, the traditional approach has been thoracotomy, tracheobronchial (sleeve) resection with various forms of reconstruction, or lobectomy depending on the location, extent of the lesion, and condition of the distal airway. Since these lesions are benign in nature, palliation with laser resection can be carried out without significant morbidity.

Certain lesions (especially papillomas) may be locally recurrent. They often require repeated laser resections but this is less invasive than a thoracotomy. However, surgical resection may still be the best option under certain situations. A combination approach may be appropriate wherein initial laser resection is carried out and lobectomv is subsequently carried out for complete cure of the remaining lesion. Conversely, after incomplete removal by surgical resection, laser vaporization may be carried out for remaining or locally recurrent tumor.

CONCLUSION

We present our experience with benign tumors of the tracheobronchial tree. This series may be considered relatively small; however, it is one of the largest series reported to date. We have described the typical endoscopic appearance and behavior of these lesions. Obviously exceptions will occur. In general, patients with these lesions are excellent candidates for Nd-YAG laser resection. Total removal of the lesions is frequently achieved, and relief of symptoms is often immediate. Loss of lung tissue and the immediate and remote sequelae of thoracotomy are avoided. When lesions are incompletely removed, repeated procedures may be needed, but, these are not usually difflcult to perform and do not usually entail increased morbidity for the patient. In fact, this may be the only option in some patients. None of our patients needed postlaser thoracotomy because of uncontrollable spread or complications.

Skilled recognition of the endoscopic appearance and behavior of these benign airwav tumors is necessary. Careful laser resection may allow the bronchoscopist to cure or e ffectively pailiate these lesions without entailing significant morbidity or mortality for the patient.

ACKNOWLEDGMENTS: The authors are grateful for the critical comments from Drs. Stephan Kamholz, Philip Stern, Peter J.P. Finch, Urmila Shivaram, and George G. Burton. We are also indebted to Rosetta Reid and Flossie Hodgson for secretarial as sistance without w hose assistance this manuscript would not have been possible.

[Figure 1 to 4 ILLUSTRATION OMITTED

(*) From the Respiratory Services, Kettering Medical Center, Dayton, Ohio (Dr. Shah); the Laser Center of the Sainte-Marguerite Hospital, Marseille, France (Drs. Garbe, Nussbaum. and Dumon); and the Center for Respiratory Endoscopy and Laser Therapy, Spedali-Civili, Brescia. Italy (Drs. Chiodera and Cavaliere). This work was done while Dr. Shah was a Visiting Fellow at the Laser Center of the Sainte-Marguerite Hospital, Marseille, France.

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Manuscript received September 7, 1993; revision accepted September 21, 1994.

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