Bronchial Adenoma. Clinical Material
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1 Robert E. Miller, Col, and Alan R. Hopeman, Col, both MC, USA (Ret) ABSTRACT Thirty-three patients with bronchial adenoma have been treated in U.S. Army hospitals. These included 27 with carcinoid, 3 with mucoepidermoid carcinoma, and 3 with adenoid cystic carcinoma. No deaths could be directly related to the adenomas during an average follow-up of 14.5 years. T he experience of the Memorial Cancer Center [ 11 portrays bronchial adenoma - including bronchial carcinoid, mucoepidermoid carcinoma, and adenoid cystic carcinoma - as a rapidly developing lesion with a disc :ouraging 5-year survival rate. Others [2-4, 12,201 have characterized the lesions as showing slow growth, local extension, and. rare distant metastases and having a 5-year survival rate of 75 to 94%. The purpose of this report is to record an experience with bronchial adenoma in which no deaths could be directly related to the virulence of the malignancy. Clinical Material Thirty-three patients were treated for bronchial adenoma from 1945 to the present in five Army hospitals: 25 at Fitzsimons Army Medical Center, 4 at Letterman Army Medical Center, 2 at Tripler Army Medical Center, 1 at Walter Reed Army Medical Center, and 1 at Martin Army Hospital. Twenty-seven had carcinoid, 3 had mucoepidermoid carcinoma, and 3 had adenoid cystic carcinoma. The average age and sex distribution of the patients is shown in Table 1. There were 31 whites and 2 blacks. The symptoms when the patients were first seen included, in order of frequency, cough, recurrent pneumonia, hemoptysis, fever, and chest pain (Table 2). One patient was asymptomatic; the lesion was detected on routine chest roentgenogram. Four patients complained of hemoptysis as the only symptom. Four had had symptoms present for 1.5,4,5, and 10 years, respectively, while the remaining patients had had symptoms for less than 1 year. A diagnosis was made by bronchoscopy with biopsy in 8 patients. Biopsy of the mucosa overlying the tumor revealed chronic inflammatory bronchitis in 3 patients. In the remaining 22 patients the lesion was not visualized or biopsied. The sites of tumor (Figure) were almost equally distributed between the right and left lung with a slight predilection for the lower lobes. From the Department of Surgery, Fitzsimons Army Medical Center, Denver, Colo. We are grateful to Thomas G. Nelson, Col, Thomas J. Whelan, Jr., BG, and Arthur Cohen, Col, all MC, USA (Ret) for their assistance in collecting the material presented. We also wish to acknowledge the assistance of Mrs. Dell Benabese and Mrs. Doris Wiggins in the preparation of this paper. Accepted for publication Dec. 4, Address reprint requests to Dr. Miller, The Longmont Clinic, 1925 Mountain View Ave., Longmont, Colo THE ANNALS OF THORACIC SURGERY
2 TABLE 1. AGE AND SEX DISTRIBUTION OF 33 PATIENTS WITH BRONCHIAL ADENOMA Average Age Sex Type of Adenoma No. of Patients (Range) Male Female Carcinoid (11-65) 22 5 Mucoepidermoid carcinoma 3 21 (12-30) 2 1 Adenoid cystic carcinoma 3 41 (37-51) 1 2 All 33 patients were treated by resection (Table 3). One patient had a wedge resection and another had segmental resection, leaving the superior segment of the left lower lobe. All patients with adenoid cystic carcinoma had central lesions requiring pneumonectomy. Postoperative irradiation was used in the treatment of 2 patients with positive nodes. Lymph node metastases were found in 3 patients with bronchial carcinoid and 2 with adenoid cystic carcinoma; none were found in patients with mucoepidermoid carcinoma. No recurrences were observed in patients who had carcinoid adenoma or mucoepidermoid carcinoma, although 2 patients had recurrences of adenoid cystic carcinoma at 6 and 11 years, respectively. Survival statistics are shown in Table 4 and causes of death in Table 5. During the period of observation, 3 patients developed new malignancies (thyroid, breast, and kidney). Bronchial carcinoid syndrome was not observed in any of the 33 patients. Because of the perplexing problem of managing bronchial carcinoid with lymph node metastases, the following patients are discussed. CASE HISTORIES Patient 1. A 30-year-old man was admitted on December 10, 1945, for evaluation of an asymptomatic left pulmonary lesion detected on routine chest roentgenogram. Bronchoscopy revealed a left lower lobe lesion, but biopsy attempts were unsuccessful in establishing a preoperative diagnosis. A left lower lobectomy was performed and a diagnosis of bronchogenic adenocarcinoma with regional lymph node metastases was made. Radiation therapy, given in two courses, was completed in July and September, In January, 1947, chest roentgenograms revealed an increase in the density of the left lower lung field, and radiation therapy was again instituted. In September, 1947, the patient TABLE 2. SYMPTOMS IN 33 PATIENTS WITH BRONCHIAL ADENOMA Symptom Cough Recurrent pneumonia Hemoptysis Fever Chest pain No. of Patients VOL. 19. NO. 4, APRIL,
3 MILLER AND HOPEMAN Distribution of adenomas in 33 patients: Right side, 17 cases; left side, 16 cases. complained of a nonproductive cough and weight gain. Chest films revealed an increase in pleural fluid, and bronchoscopy revealed an extrinsic mass encroaching on the lumen of the left upper lobe bronchus. Radiation therapy was again instituted. Clinical signs of constrictive pericarditis precipitated operative intervention, which was unsuccessful. Postmortem examination revealed constrictive pericarditis secondary to radiation therapy; no tumor was present. Review of the original tissue by the Army Medical Museum revealed the lesion to be a bronchial adenoma, carcinoid ty Pe. When a regional lymph node contains metastatic bronchial carcinoid in a left lower lobectomy specimen, as in this patient, it would be uncertain whether or not there was tumor in the remaining portion of the left lung. Therefore, with a final diagnosis of bronchial adenoma at the time of operation, we would recommend a complete pneumonectomy and hilar lymphadenectomy to eradicate the lesion. Patient 2. A 19-year-old man was admitted on May 9, 1966, for evaluation of recurrent middle lobe pneumonia. Bronchoscopy revealed extrinsic pressure on the middle lobe bronchus. After evaluation, a middle lobectomy was performed. A bronchial carcinoid accounted for the extrinsic pressure, and regional lymph nodes contained metastatic tumor. A right lower lobectomy and lymphadenectomy of the right bronchus were performed; the lymph nodes again TABLE 3. TREATMENT IN 33 PATIENTS WITH BRONCHIAL ADENOMA Type of Adenoma Treatment No. of Patients Carcinoid (27 patients) Pneumonectomy Bilobectomy Lobectomy Segmental resection Wedge resection Mucoepidermoid carcinoma Bilobectomy (3 patients) Lobectomy Adenoid cystic carcinoma Pneumonectomy (3 patients) THE ANNALS OF THORACIC SURGERY
4 TABLE 4. LENGTH OF SURVIVAL IN 33 PATIENTS WITH BRONCHIAL ADENOMA Type of Adenoma Average Survival (Yr) Range Carcinoid (27 patients) yr Mucoepidermoid carcinoma yr (3 patients) Adenoid cystic carcinoma hr- 15 yr (3 patients) contained metastatic bronchial carcinoid. A complete pneumonectomy and mediastinal lymph node dissection were accomplished at a later date, at which time no tumor was found in the resected nodes or specimens. The patient was thereafter medically retired and was performing normal activities as an aircraft mechanic as of July 10, This patient underwent staged operations to remove the tumor, while we simultaneously attempted to preserve maximal pulmonary function. In retrospect, we believe that the second operation eradicated the tumor, although the complete pneumonectomy and lymphadenectomy were the only means of assuring total extirpation of the disease. Patient 3. A 23-year-old woman was admitted on October 19, 1970, for evaluation of hemoptysis of 4 months duration. A chest roentgenogram revealed a solitary lesion in the right lower lobe, and bronchography demonstrated occlusion of the posterior basilar segmental bronchus. During the course of a right lower lobectomy, a lymph node in the minor fissure was found 2 cm from the tumor. Pathological examination by frozen section revealed reactive hyperplasia in the lymph node and bronchial carcinoid in the pulmonary tumor. Permanent histological sections showed a focus of metastatic bronchial carcinoid in the lymph node. The patient had a benign postoperative course and was performing normal activities as of April, 1974, with no roentgenographic abnormalities. TABLE 5. CAUSE OF DEATH AFTER OPERATION IN 6 PATIENTS WITH BRONCHIAL ADENOMA Time after Operation Cause of Death CARClNOlD 16 yr Renal failure 16 yr Acute hemorrhagic pneumonitis 12 yr Subarachnoid hemorrhage 1.5 yr Constrictive pericarditis secondary to irradiation ADENOID CYSTIC CARCINOMA 12 hr 13 yr Pulmonary edema Pulmonary insufficiency 8c pneumonitis VOL. 19, NO. 4, APRIL,
5 MILLER AND HOPEMAN The involvement of adjacent pulmonary tissue and other lymph nodes with metastatic bronchial carcinoid is unknown. To assure complete local resection, a middle lobectomy and lymphadenectomy of the right bronchus would be recommended. If metastatic foci were found, further resection would be indicated, as in Patient 2, since despite careful follow-up, roentgenographic changes might not fully document growth of the carcinoid before it became unresectable. Comment Bronchial adenoma has been a useful term for identifying those pulmonary lesions having a malignant potential but a less aggressive nature than bronchogenic carcinoma. The terms bronchial carcinoid, mucoepidermoid carcinoma, and adenoid cystic carcinoma must be used for any meaningful discussion of these tumors. BRONCHIAL CARCINOID The first clinically diagnosed bronchial carcinoid was described by Kramer 171 in 1930, although Laennec [8] recognized the lesion in Carcinoid tumors have a slight predilection for the lower lobes. Most lesions are visible by bronchoscopy, but peripheral as well as multiple lesions occur. Distant metastases or regional lymph node involvement occurs in approximately 12% of cases [lo]. Most reports [2-4, 12, 201 indicate that bronchial carcinoid grows slowly, has a low potential for malignancy, and allows long-term survival. A recent report [ 191, however, revealed a dismal 5-year survival rate of 59%. To explain the different results, specific factors will be analyzed: namely, age of the patient, stage of disease, and type of treatment. Since most reports on bronchial adenoma do not evaluate the specific types but present the data collectively, exact evaluations are impossible. The average age range in five series [2-4, 12, 201 was 40 to 49 years for all patients with bronchial adenoma. The average age for patients with bronchial carcinoid in the series reported by Turnbull and associates [ 191 was 49 years. In our 27 patients the average age was 30 years. Age seems to play a minor role in survival with carcinoid adenomas. In Turnbull and associates series [ 191 the span of treatment encompassed the years from 1926 to Of the 44 patients with carcinoid, only 27 had thoracotomies. There were 24 resections, 7 pneumonectomies, 14 lobectomies, and 3 wedge or segmental resections. The 5-year survival was 59%. In the series of Wilkins and co-workers [20], the span of treatment encompassed the years from 1909 to Only 67 of 82 lesions were resected. All 57 patients with carcinoid adenoma who were explored underwent resection. There were 14 pneumonectomies, 16 bilobectomies, 23 lobectomies, and 4 lesser resections. The 5-year survival was 75%. In our series all patients underwent resection, and only 3 required pneumonectomy. Patients in Turnbull s [19] and Wilkins [20] series were treated with fulguration and radiation for tumors that would now be considered for resection. Not all 382 THE ANNALS OF THORACIC SURGERY
6 patients in their series who had exploratory operations underwent resection, and greater parenchymal resections probably indicated more advanced disease. McBurney, Kirklin, and Woolner [ 101 reviewed 700 patients with bronchial adenoma up to 1952 and found 87 with metastatic disease. In thirteen articles since that time 79 metastasizing lesions were found in 645 patients. Again the type of adenoma was not always identified; however, approximately one-third of the metastatic lesions in patients reported up through 1952 were adenoid cystic carcinomas. If we realize that approximately 12% of the lesions will metastasize, we must perform adequate resection and carefully examine the resected specimen to insure complete removal of the tumor. If there is any metastatic disease, further resection should be done. ADENOID CYSTIC CARCINOMA Hamper1 [6] described adenoid cystic carcinoma (cylindroma) in This tumor is more aggressive and has a greater propensity for recurrence. Adenoid cystic carcinoma occurs more centrally than carcinoid and more frequently spreads to regional lymph nodes. There is a general consensus that the malignant potential of the tumor is formidable [9, 12, MUCOEPIDERMOID CARCINOMA Mucoepidermoid carcinoma was described in 1952 by Smetana [161 as the third variety of endobronchial neoplasm. A patient in this series, 1 of 2 initially described by Dr. Smetana, is alive and well as of April, 1974, 23 years after operation. Payne and colleagues [ 141 and Meckstroth and co-workers 1111 considered these tumors almost benign. In 1966, Reichle and Rosemond [ 151 reviewed 29 patients and reported no recurrence when the tumor had been completely resected. Ozlu [IS] and Dowling [5] and their co-workers discussed the first patients dying from metastatic mucoepidermoid carcinoma of the lung. Twelve patients presented by Turnbull and associates [ 191 constitute the largest series of patients with mucoepidermoid carcinoma reported. All these patients died from their disease within 18 months. Axelsson, Burcharth, and Johansen [ 11 concluded that this is a malignant lesion that grows rapidly, and they recommend radical resection. Approximately 50 patients with mucoepidermoid carcinoma have been reported in the English literature. Any conclusions drawn from this small number of cases are tentative, although some generalizations do seem apparent. The inconsistency in the degree of malignancy can best be explained by noting the age of the patient and the stage of the disease when treated. In the Turnbull and Axelsson series the average age was 59 and 61 years, respectively. In Reichle s review the average age was 45 years, and among our 3 patients it was 2 1. In Turnbull s series of 12 patients, 7 had exploratory operations; 3 had a pneumonectomy, 1 a lobectomy, and 3 were unresectable. Six patients who had preoperative localized disease survived operation but later died of widespread metastatic disease. Five patients had metastatic disease on admission and were treated symptomatically. Of the 4 patients in Axelsson s series who had exploratory operations, 2 had a pneumonectomy and 1 a lobectomy. Two patients were free of disease in a short VOL. 19, NO. 4, APRIL
7 MILLER AND HOPEMAN follow-up and 1 died in the postoperative period with no residual disease. One patient had unresectable disease and died 5 months postoperatively. In Reichle's review of 29 patients, 6 had a pneumonectomy and 13 had either lobectomy, bilobectomy, or segmental resection. Two patients had endoscopic resection and 6 received irradiation or conservative treatment. In 2 the treatment was not recorded. Of the latter 6, the average age was 55. The 3 patients in our series had no nodal involvement and underwent lobectomy or bilobectomy. All patients are now living and well. Conclusion Symptoms of persistent cough, hemoptysis, fever, chest pain, and recurrent pneumonia should stimulate aggressive diagnostic investigation. If lesions are found during bronchoscopy, biopsy should be performed. The vascularity of these lesions should not deter biopsy, but rather incite the endoscopist to careful observation and management. From the material presented, it is evident that the survival rate is higher in younger patients and less parenchymal resection is required to eradicate the tumor. Long-term follow-up is essential, not only to better understand the disease entities, but to aid early detection of unrelated malignancies 19, 19, 201. Bronchial carcinoid, mucoepidermoid carcinoma, and adenoid cystic carcinoma must be considered as separate entities. Ref rences 1. Axelsson, C., Burcharth, F., and Johansen, A. Mucoepidermoid lung tumors. J Thorac Cardwvasc Surg 65:902, Batson, J. F., Gale, J. W., and Hickey, R. C. Bronchial adenomata: A clinical resume. Arch Surg 92:623, Bower, G. Bronchial adenoma: A review of 28 cases. Am Rev Resp Dis 92:558, Donahue, J. K., Weichert, R. F., and Ochsner, J. L. Bronchial adenoma. Ann Surg 167:873, Dowling, E. A., Miller, R. E., Johnson, I. M., and Collier, S. C. D. Mucoepidermoid tumors of bronchus. Surgery 52:600, Hamperl, W. Uber gutartige bronchial Tumoren (Cylindroma und Carcinoide). Virchows Arch Pathol Anat 300:46, Kramer, R. Adenoma of bronchus. Am Otol39:689, Laennec, R. T. H. Trait6 de l'auscultation mediate et des maladies des poumons et du coeur (3d ed). Paris: Chaud, Vol 1, p Logan, W. D., Jr., Sehdena, J., Hatcher, C. R., and Abbott, 0. A. Tracheobronchial adenomas. Am Surg 36:359, McBurney, R. P., Kirklin, W., and Woolner, L. B. Metastasizing bronchial adenomas. Surg Gynecol Obstet 96:482, Meckstroth, C. V., Davidson, H. B., and Kress, G. 0. Mucoepidermoid tumor of the bronchus. Chest 40:652, OGrady, W. P., McDivitt, R. W., Holman, C. W., and Moore, S. W. Bronchial adenoma. Arch Surg 101:558, Ozlu, C., Christopherson, W. M., and Allen, J. D., Jr. Mucoepidermoid tuiiiorsof the bronchus. J Thorac Cardiouasc Surg 42:24, Payne, W. S., Ellis, F. H., Jr., Woolner, L. B., and Moersch, H. J. The surgical treatment of cylindroma (adenoid cystic carcinoma) and mucoepidermoid tumors of the bronchus. J Thorac Cardiouasc Surg 38:709, I 384 THE ANNALS OF THORACIC SURGERY
8 15. Rkchle, F. A., and Rosemond, G. P. Mucoepidermoid tumors of the bronchus. J Thorac Cardwvasc Surg 51:443, Smetana, H. F. Quoted by A. A. Liebow in Tumors of the Lower Respiratory Tract. In Atlas of Tumor Pathology, Sect V, Fasc Washington, D.C.: Armed Forces Institute of Pathology, Takita, H., Vincent, D. G., and Adler, R. H. Bronchial adenoma. NJ State J Med 71:563, Toole, A. L., and Stern, H. Carcinoid and adenoid cystic carcinoma of the bronchus. Ann Thorac Surg 13:63, Turnbull, A. D., Huvos, A. G., Goodner, J. T., and Beattie, E. J., Jr. The malignant potential of bronchial adenoma. Ann Thorac Surg 14:453, Wilkins, E. W., Darling, R. C., Soulter, L., and Sniffen, R. C. A continuing clinical survey of adenomas of the trachea and bronchus in a general hospital. J Thorac Cardiovasc Surg 46:279, NOTICE FROM THE SOUTHERN THORACIC SURGICAL ASSOCIATION The Twenty-second Annual Meeting of the Southern Thoracic Surgical Association will be held at the Fairmont-Roosevelt Hotel, New Orleans, La., on November 6-8, Reservations may be made by writing to the Reservations Manager, Fairmont-Roosevelt Hotel, New Orleans, La. Members wishing to participate in the scientific program should submit abstracts - typed double-spaced and in triplicate - to David C. Sabiston, Jr., M.D. [Chairman of the Program Committee], Duke University Medical Center, Durham, N.C The deadline for submission of abstracts is June 1, The Council of the Southern Thoracic Surgical Association has ruled that all slides used during presentation of papers and discussions must be of 35-mm size. If additional information is required, inquiries should be directed to Dr. Sabiston. Application for membership in the Southern Thoracic Surgical Association, on forms provided by the Association, should be sent directly to J. Alex Hailer, Jr., M.D. [Chairman of the Membership Committee], The Johns Hopkins Hospital, Baltimore, Md The deadline for application to membership is September 1, Papers that are accepted for the program will be considered for publication in The Annals and must be submitted to the Editor by October 15, JAMES W. BROOKS, M.D. Secretary-Treasurer VOL. 19, NO. 4, APRIL,
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