Preferred Surgical Treatment for Alveolar Cell Caranoma
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1 Preferred Surgical Treatment for Alveolar Cell Caranoma Edwin C. James, LTC, George F. Schuchmann, LTC, Roger V. Hall, MAJ, James R. Patterson, MAJ, James T. Gillespie, COL, and Alphonse C. Gomez, COL, all MC, USA ABSTRACT An analysis of our experience with patients having bronchiolar or alveolar cell carcinoma is reported. The remarkable biological variability of this peripheral tumor has important surgical implications. Basically, two dominant clinical presentations occur. In the less common diffuse or multinodular form, prolonged survival is infrequent regardless of the therapeutic approach. Often these patients die from respiratory compromise due to the tumor itself. In the more common localized or solitary form the prognosis for cure is good, approximating 7% or higher. Based on the material presented, lobectomy is the preferred method of surgical treatment. In patients manifesting multinodular disease, surgical resection rarely seems warranted. The concept of preserving pulmonary tissue is stressed. Since its initial description by Malassez [ in 76, bronchiolar or alveolar cell carcinoma has been something of an enigma in the overall framework of bronchogenic carcinoma. Although metastatic glandular cancers manifest a similar histological appearance [], most authors accept that this tumor s primary origin is the lung [l-3,,,9]. Still, the specific site, cell, or mode of pathogenesis remains uncertain [lo]. From the Departments of Surgery at Madigan, Fitzsimons, and Letterman Army Medical Centers, Tacoma, WA, Denver, CO, and San Francisco, CA, respectively. The views and opinions expressed herein do not necessarily represent those of the Surgeon General, the Department of the Army, or the Department of Defense. Supported by the Clinical Research Service, Madigan Army Medical Center, Tacoma, WA. We acknowledge with appreciation the helpful assistance of the following persons in reviewing the pathological material: Keith Hallman, M.D., Chief of Anatomical Pathology, Madigan Army Medical Center; Gist Farr, M.D., Chief of Anatomical Pathology, Letterman Army Medical Center; John T. Gmelich, M.D., Chief of Anatomical Pathology, Veterans Administration Hospital, San Diego; and Julian T. Coggin, M.D., Assistant Chief, Department of Pathology, Fitzsimons Army Medical Center. Address reprint requests to Dr. James, Department of Surgery, West Virginia University Medical Center, Morgantown, WV 606. The remarkable biological variability exhibited by this peripheral tumor has important surgical implications. Basically, two dominant clinical presentations occur. In the less common diffuse or multinodular form (Fig l), prolonged survival is unusual regardless of the therapeutic approach; these patients commonly die from respiratory compromise due to the tumor itself. Fortunately, the more frequent localized form arises as a solitary pulmonary nodule (Fig ), for which the prognosis for cure is good. The distinction between the two clinical variants is not always clear, however, and patients with multinodular disease are sometimes subjected to harmful surgical resection. We have reviewed our experience with this disease in an attempt to determine a preferred method of management. Clinical Material and Results From 9 through 973, patients with alveolar cell carcinoma were recorded in the tumor registries at Madigan, Fitzsimons, and Letterman Army Medical Centers. Although most of the tumors were confirmed initially by the Armed Forces Institute of Pathology, all records and available microscopical material were reexamined. Subsequently, 0 cases were excluded because of disagreement with the diagnoses or insufficient material for review. Therefore cases, for an incidence of 3.% among,3 patients with bronchogenic carcinoma, constitute the basis for this report. Interestingly, a previously reported patient with cavitary bronchiolar carcinoma associated with an intracavitary aspergilloma [] was not included because of inability to substantiate this diagnosis. Men predominated by a ratio of.7 to (3 to 3). Ages ranged from to 77 years with a mean of 6.6 years. Of the patients, 7 were white and was black. Although a history of smoking was identified in 3 patients (6.6%), it was dis- 7
2 The Annals of Thoracic Surgery Vol No August 976 A B Fig I. Abnormal chest roentgenograms showing (A) moderate bilateral multinodularity and (B) diffuse bilateral multinodularity. Fig. Abnormal chest roentgenogram shozoing isolated peripheral nodule (arrow) in right upper lobe. Patient is alive and free from disease 7 years, 9 months following lobectomy. tinctly absent in (0.%) and unknown in others ( %). Results of chest roentgenograms in 7 patients are categorized according to isolated or diffuse nodularity in Table. One patient died from an acute myocardial infarction before a chest roentgenogram was obtained, and alveolar cell carcinoma in the right upper lobe was an incidental finding at postmortem examination. In 3 cases (7.%) a solitary peripheral lesion was either solid (0 patients, 7.%), cavitary ( patient,.9%), or infiltrative ( patients, 0%) in appearance. Calcification was recognized in of the 3 cases (.7%). Nodule diameter was estimated in 3 patients only and varied from. to 7.0 cm with a mean size of. cm. Twenty-two nodules (6.9%) were situated in upper lobes, with the lower lobes next in frequency and the middle lobe and lingula least often involved. Finally, in patients (.%) chest roentgenograms demonstrated evidence of either unilateral or bilateral diffuse nodularity that proved to be bilateral in the majority at postmortem examination. Details of the clinical manifestations in these patients are summarized in Table. Seventeen patients (3. %) were asymptomatic. Frequently the alveolar cell carcinoma was identified during evaluation of another medical problem. A productive or dry cough occurred in
3 9 James et al: Treatment of Alveolar Cell Carcinoma Table. Roentgenographic Findings in 7 Patients with Alveolar Cell Carcinoma Solitary Nodules (7.%) Diffuse Nodules (.%) Site of No. of Nodules Patients Solid Cavitary Infiltrative Right Lung Bilateral RUL 3 RML 3 RLL 3 LUL 9 Lingula LLL Total 7 0 RUL = right upper lobe; RML = right middle lobe; RLL = right lower lobe; LUL = left upper lobe; LLL = left lower lobe. instances (.%); chest pain in (%); dyspnea in 0 (0.%); and hemoptysis in only (.3%). Upper respiratory tract infection or pneumonia was a significant clinical feature in 0 instances (0.%). Symptoms or signs related to the tumor portended an ominous outlook. However, patient with initially localized disease survived longer than five years without treatment and during the last two years was known to have metastatic disease (Fig 3). Multiple diagnostic methods were of variable Table. Clinical Manifestations in Patients with Alveolar Cell Carcinoma Sign or Symptom Asymptomatic Chest pain Productive cough Dry cough Dyspnea Weight loss Pneumonia Hemoptysis Upper respiratory infection Pleural effusion Anorexia Cachexia Hoarseness Bone pain Fatigue No. of Patientsa 7 0 "Several patients exhibited multiple signs or symptoms. success. Sputum cytology produced a positive yield in 7 of 3 patients (6.3%) and bronchoscopy was diagnostic in of 3 (.O/o). With the suggestion of adenopathy, supraclavicular or scalene node biopsy yielded positive results in 3 of cases (37.%). In 3 patients with pleural effusions, cytology or pleural biopsy was highly suspicious for malignancy in instances (66.7%). Mediastinoscopy provided a positive biopsy the single time it was employed. Nine patients had their alveolar cell carcinoma first documented at postmortem examination. Primarily on the basis of infiltrative characteristics on chest roentgenograms, a presumptive diagnosis of tuberculosis was made in 7 patients (.6%). Antituberculosis treatment was utilized in all 7, and 3 subsequently had positive cultures for mycobacteria coexistent with alveolar cell carcinoma. Another patients (.3 O/O) had carcinomas identified in association with nonspecific pulmonary scars. Additionally, patients (.%) exhibited hamartomas in close proximity to carcinomas in the upper lobes, and another patient (.%) had a closely associated sarcoid granuloma. Altogether, 0 of the patients (0.%) demonstrated alveolar cell carcinoma in areas of coexistent or previously diseased lung. Thirty-seven operations were performed in 3 patients (Table 3) with operative death (.9%). This resulted from respiratory insufficiency on the thirty-seventh postoperative day following right pneumonectomy in a patient with the mul-
4 60 The Annals of Thoracic Surgery Vol No August 976 A Fig 3. (A) Abnormal chest roentgenogram showing isolated peripheral nodule (arrow) in right midlung field. (B) Chest roentgenogram two and one-half years later shows multinodularity. This patient survived five years without any form of treatment. 3. Results Of 37 Operations in 3 Patients Operative Procedure RU lobectomy LU lobectomy LL lobectomy RM & RL bilobectomy RL lobectomy RM lobectomy RU & RM bilobectomy R pneumonectomy Wedge resection, LLL Wedge resection, RUL Thoracotomy, biopsy only No. Of Operations RU = right upper; LU = left upper; LL = left lower; RM = right middle; RL = right lower; R = right. B tinodular form of the disease. Unsuccessful second surgical procedures for residual carcinoma consisted of wedge resection Iof the opposite upper lobe after an initial left upper lobectomy and completion pneumonectomy following an initial right lower lobectomy. Both patients experienced progressive respiratory impairment, and their survival was extended for only a matter of months. Of the entire patients, 3 (7.%) survived five years or longer and were ostensibly cured (Table, Groups B and F). After resection of isolated peripheral nodules, of them died from coronary occlusion without dettxtable cancer at and months, respectively. In addition, others succumbed to subsequent primary bronchogenic carcinomas of different histology (undifferentiated and mixed adenosquamous) at 9 and 3 months, respectively (Group F). Therefore 9 patients (.%) remained alive and cured 60 to months following lobectomy (Group B). Also, patients (.3%) were alive at 3 to 9 months without evident disease (Group C). One patient initially diagnosed at tlioracotomy and biopsy only as manifesting pulmonary adenomatosis remained alive at 0 months with diffuse disease. This patient reflects reasonable survival with diffuse disease when critical pulmonary tissue is not resected. The
5 6 James et al: Treatment of Alveolar Cell Carcinoma Table. Outcome in Patients with Alveolar Cell Carcinoma Result A: Alive with disease B: Alive without disease 9 (over years) C: Alive without disease (under years) D: Dead with disease (related) E: Dead with disease F: (unrelated) Dead without disease (over years) G: Dead without disease (under years) No. of Patients patients who had multinodular disease roentgenographically when they were first seen died within relatively short intervals following diagnosis except for the one who progressed from localized to diffuse disease after three years. In several cases the diagnosis of diffuse alveolar cell carcinoma was suspected but not proved until after death. Of the 3 patients with roentgenographically apparent isolated peripheral nodules, the diagnosis was an incidental postmortem finding in who died from other disease processes (Group E). Excluding these patients and the individual misdiagnosed as having pulmonary adenomatosis, the 3 long-term survivors signify a fiveyear survival rate of 0.6% (3 of 3) among patients with disease that was favorable roentgenographically. If additional patients (Group G) are included who had no residual cancer when examined postmortem and who died of suicide and a myocardial infarction at and months, respectively, the total number cured in this category totals of 3 patients (6.9 yo). Comment Reports from the Armed Forces Institute of Pathology frequently emphasize that alveolar cell carcinoma is most often first seen as a solitary pulmonary lesion. With localized disease, curative resection should afford excellent survival [,6. In contrast, patients with multinodular disease seldom benefit from surgical intervention [,,,3]. Their ultimate fate often makes the preservation of pulmonary tissue an important concept. An analysis of the cancer-related deaths (Table, Group D) reveals that of these patients (.%) progressed to terminal respiratory impairment. Three others (.%) manifested pericardial metastases and cardiac tamponade as the primary cause of death. In patients demonstrating more than localized disease at thoracotomy, survival was adversely influenced by any form of extended resection (ie, bilobectomy, pneumonectomy, completion pneumonectomy). All these patients died from their disease, and residual pulmonary cancer was proved postmortem. Two biological features favoring cure in alveolar cell carcinoma are the potential for slow growth and the tendency for the tumor to remain localized [l,, 6. Once lymph node permeation takes place or satellite lesions appear, the likelihood of a favorable outcome is remote. Although isolated metastases to the same lung occur, this usually implies spread to the opposite lung and more distant sites. For proper surgical treatment, it is important to distinguish localized and curable disease from its multinodular and probably incurable counterpart. In patients with multinodular disease that remains unrecognized until thoracotomy, surgical resection becomes a matter of combined philosophy and experience. Certainly the results recorded in this series and by Fitzpatrick and colleagues 6 suggest that resections in excess of lobectomy are rarely indicated; actually, by removing critical pulmonary tissue, they may prove harmful. All patients who were cured in either series underwent lobectomy for localized peripheral disease. We recommend an aggressive attitude toward undiagnosed solitary pulmonary lesions whether they are solid, cavitary, or infiltrative in appearance. Alveolar cell carcinoma in association with previous, suspected, or coexistent pulmonary disease occurred in 0 (0.%) of our patients. Inflammatory or scarring conditions of the lung exhibiting roentgenographic progression should arouse the suspicion of malignancy. Noninvasive mediastinal laminagrams [7] are useful in assessing the status of the medias-
6 6 The Annals of Thoracic Surgery VoI No August 976 tinum. Frequently we add full-lung laminagrams of the lesion to check for additional disease. Eventually many patients with solitary peripheral carcinomas require thoracotomy for diagnosis. For disease that is benign grossly a wedge resection is performed for histological examination, followed by lobectomy if the lesion proves to be malignant. However, most patients undergo immediate lobectomy as the initial and only operative procedure. In patients demonstrating more than one pulmonary nodule, pleural seeding, or mediastinal tumor extension, biopsy alone is performed. In most instances these features indicate a behavioral alteration inconsistent with surgical cure. In addition, the quality of survival is improved with the preservation of pulmonary tissue. References Amay IS: Bronchiolar (alveolar cell) carcinoma: failure to cause symptoms for more than years. Am Rev Tuberc 7:63, 9 Belgrad R, Good CA, Woolner LB: Alveolar-cell carcinoma (terminal bronchiolar carcinoma): a study of surgically excised tumors with special emphasis on localized lesions. Radiology 79:79, 96 Bell JW, Knudtson KP: Observations on the natural history of bronchiolo-alveolar cell carcinoma: experience with twenty-one cases. Am Rev Resp Dis 3:660, 96 Cooley WE, Silverman S: Radiation therapy in bronchiolar-alveolar cell carcinoma: a case report. Cancer 3:077, 97. Delarue NC, Anderson W, Sanders D, et al: Bronchiolo-alveolar carcinoma: a reappraisal after years. Cancer 9:90, Fitzpatrick HF, Miller RE, Edgar MS Jr, et al: Bronchiolar carcinoma of the lung: a review of 33 patients. J Thorac Cardiovasc Surg :30, James EC, Ellwood RA: Mediastinoscopy and mediastinal roentgenology: a clinical correlation. Ann Thorac Surg :3, 97. Knudson RJ, Hatch HB, Mitchell WT Jr, et al. Unusual cancer of the lung:. Elronchiolar carcinoma of the lung. Dis Chest :6, Kress MB, Allan WB: Bronchiolo-alveolar tumors of the lung. Bull Johns Hopkins Hosp :, Kuhn CS: Fine structure of bronchiolo-alveolar cell carcinoma. Cancer 30:07, 97. Malassez L: Examen histologique d un cas de cancer encophaloide du poumon (epithelioma). Arch Physiol Norm Path0 3:33, 76. Mays EE, Hawkins JA: Cavitary bronchiolar carcinoma with an intracavitary aspergilloma. Am Rev Resp Dis 9:06, Munnell RE, Lawson RC, Keller DF: Solitary bronchiolar (alveolar cell) Carcinoma of the lung. J Thorac Cardiovasc Surg :6, 966. Rosenblatt MB, Lisa JR, Collier F: Primary and metastatic bronchiolo-alveolar carcinoma. Dis Chest :7, 967. Southworth RR, Becker A: Bronchiolar carcinoma (pulmonary adenomatosis). Ann Intern Med :3, Woodruff JH Jr, Ottoman RE, Isaac F: Bronchiolar-cell carcinoma. Radiology 70:33, 9
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