Benign Localized Pleural Mesotheliomas Presenting as Arthritis
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1 Benign Localized Pleural Mesotheliomas Presenting as Arthritis Allen S. Hudspeth, M.D. P rimary tumors of the pleura are relatively rare, but they present many interesting pathological and clinical features. In spite of significant advancements in the understanding of pleural tumor pathology fostered by Klemperer and Rabin [8], Stout et al. [ll, 121, Clagett and associates [3], and Benoit and Ackerman [2], there is still no general agreement as to the proper classification of these tumors or clear correlation between their histological appearance and clinical behavior. However, segregation of pleural tumors into two main clinical groups-diffuse and localized-seems justified and is helpful. In general, the diffuse tumors are malignant and localized tumors are benign or intermediate in their behavioral characteristics. The diffuse pleural tumor usually involves large portions of the pleural cavity and often may encase the entire lung. Patients commonly complain of weakness, chest pain, dyspnea, and rapid weight loss. Other extrathoracic symptoms have not been reported. In general, these tumors should not be considered surgical problems since most are inoperable or can be grossly removed only by pleuropneumonectomy [5]. Long-term survival is extremely rare. This tumor has been encountered in eight patients at the North Carolina Baptist Hospital since None of these patients had extrathoracic symptoms, and none survived for two years. On the other hand, localized pleural mesotheliomas are readily amenable to surgical removal, and the overall results of this form of therapy are excellent [3, 5, 61. These localized tumors probably should be separated into benign and intermediate groups. The intermediate group is more apt to produce symptoms referable to the chest. They are less often pedunculated and may be embedded within pulmonary parenchyma. They infrequently produce extrathoracic symptoms and are prone to local recurrence following conservative resection and may even metastasize by local extension. However, the benign group of tumors rarely produces symptoms referable to the chest. They are usually very fibrous in character, are pedunculated, project freely into the pleural cavity, and can be easily resected. The benign tumors are almost always From the Bowman Gray School of Medicine, Winston-Salem, N.C. Accepted for publication Feb. 14, VOT, 2, NO. 5, SEPT.,
2 H U D S P E T H associated with a more or less characteristic pattern of signs and symptoms not yet clearly understood. The exact incidence of these tumors is not known, although they are apparently more unusual than either the malignant or intermediate variety. Four apparently typical examples of localized benign pleural mesothelioma have been treated surgically at the North Carolina Baptist Hospital since 1957, and their presentation is the purpose of this report. CASE REPORTS CASE 1 L. L., a 64-year-old white female, was referred to the North Carolina Baptist Hospital in January, 1957, for evaluation of painful swollen joints and clubbing A B c FIG, 1. Case 1. (A) Posteroanterior roentgenogram of the chest showing wellcircumscribed mass in the right side of the st. (B) Circumscribed and well-encapsuor showing n um erous bosse lations. Note the small area of fileural attachment at the center of the tumor. (C) Photomicrograph demonstrating tangled network of fibrous tissue with varying degrees of cellularity. MOO, before 40% reduction. 692 THE ANNALS OF THORACIC SURGERY
3 Mesotheliomas with Arthritis of her digits. In July, 1956, she had noted the onset of slowly progressive swelling and pain in her ankles and knees with local heat and redness. The joint symp toms had been migratory and later involved her wrists. She had been treated with various drugs without benefit. In December, 1956, she noted the onset and rapid progression of clubbing of her fingers and toes. There were no symptoms referable to the chest. The chest roentgenogram revealed a moderately large mass in the right side of the chest (Fig. 1A). Dullness to percussion and decreased breath sounds over this area were noted. The most impressive physical findings were tender swelling of her ankles, knees, and wrists, and rather profound clubbing of her digits. Clinical laboratory studies were within normal limits. Surgery was advised, and a firm, lobulated tumor was found projecting freely into the pleural space (Fig. 1B). It was attached to the lateral parietal pleura by only a very narrow vascular pedicle which could be controlled without difficulty. Microscopic study of the tumor showed a tangled network of fibrous tissue which manifested varying degrees of cellularity (Fig. 1C). There was abundant reticulin throughout. The diagnosis was mesothelioma of the pleura, benign fibrous type. All of the patient s arthritic symptoms subsided immediately following removal of the tumor. Clubbing receded slowly but had disappeared at the end of three months. She was last examined in 1962 and was asymptomatic without evidence of tumor recurrence. CASE 2 A. L., a 64-year-old white female, was admitted to the hospital in October, She had no symptoms referable to the chest. A few months prior to admission she developed migratory joint pains with tenderness and swelling and noted extreme pain in the dorsal spine with bending. She consulted a chiropractor because of her joint symptoms. He x-rayed her spine and saw a large tumor in the left side of her chest and referred her for evaluation and treatment (Fig. 2). Physical examination revealed dullness and decreased breath sounds over the left lower chest. There was swelling, tenderness, and redness of her knees and wrists. She did not have clubbing of the digits. All clinical laboratory studies were within normal limits. At surgery this tumor was hanging by a thin, narrow pedicle from the FIG. 2. Case 2. Posteroanterior roentgenogram showing sharp margin and usual density seen in localized benign pleural mesotheliomas. VOL. 2, NO. 5, SEPT.,
4 HUDSPETH anterior parietal pleura. It projected freely into the pleural cavity and was removed simply by clamping the pedicle. Grossly, the tumor was bosselated and moderately firm but resilient. Microscopically, it was very similar to that seen in Case 1 and varied only in cellularity and arrangement of fibrous tissue. It also was interpreted as a benign localized pleural mesothelioma. This patient s postoperative response was excellent, and all of her arthritic symptoms were gone by the time she awakened from anesthesia. She has been observed closely for six years and has had no further joint symptoms and no evidence of recurrence of the tumor. CASE 3 J. M., a 66-year-old white male, was admitted in December, He had been moderately disabled with joint symptoms since January, There had been painful swelling of his ankles, knees, elbows, wrists, and both hands. He had noted severe clubbing of his fingers and toes since March, In May, 1962, he had a myocardial infarction, and a chest roentgenogram revealed a mass in the left side of his chest. He was referred 18 months later because of enlargement of the tumor. There had been no symptoms referable to the mass. Physical examination revealed him to be moderately hypertensive, and there was dullness and decreased breath sounds over the left lower chest. Clinical laboratory studies, including arterial poz,.pcoz, and ph, were within normal limits. Rheumatoid factor was not present in his serum. Because this patient s signs and symptoms were associated with a circumscribed, dense mass in the chest, he was thought to have a benign localized pleura mesothelioma and surgical treatment was advised. This tumor arose from the parietal pleura over the dome of the diaphragm and projected freely into the pleura1 space. It was attached by a narrow vascular pedicle and could be excised very easily. Microscopically, the tumor was well encapsulated and was composed of interlacing bands of fibrous connective tissue with varying degrees of cellularity. This patient noted immediate improvement in his joint symptoms, and by his second postoperative day all swelling, pain, and limitation of motion had disappeared. The clubbing receded slowly over a period of eight months. He had no further joint symptoms and no recurrence of the tumor at the time of his death in December, 1964, from a second myocardial infarction. CASE 4 F. C., a 39-year-old white female was admitted in December, 1964, for evaluation and treatment of arthritis. In April, 1964, she had developed swelling of both ankles with tenderness and enlargement of her finger tips. She subsequently developed pain and tenderness of her knees, wrists, elbows, and fingers. There was associated swelling, increased heat, and redness. She had been told that she had rheumatoid arthritis and was treated with cortisone for four months without benefit. Her symptoms progressed to limitation of motion due to pain and swelling, and she had been forced to stop her job as a typist. She had no symptoms referable to the chest. Physical examination revealed only moderate clubbing; however, there was severe fusiform swelling of her fingers, wrists, feet, ankles, and knees with associated increased heat, redness, and limitation of motion. There was some decrease in the breath sounds over the lower anterior chest on the right side. The chest roentgenogram revealed an ovoid, dense mass in the right side of the chest (Fig. 3A). Clinical laboratory studies, including arterial poz, pco,, and ph, were within normal limits. Rheumatoid factor was not present in her serum. This patient also was diagnosed preoperatively as having a benign localized pleural mesothelioma. At surgery a slightly bosselated, firm tumor projected 694 THE ANNALS OF THORACIC SURGERY
5 Mesotheliomas with Arthritis A FZG. 3. Case 4. (A) Posteroanterior roentgenogram demonstrating ovoid but somewhat bosselated dense tumor in the right lower lung field. (B) Photomicrograph showing almost strictly fibrous appearance of this tumor. ~100, before 40% reduction. freely into the pleural space and was attached to the visceral pleura of the middle lobe by a thin, elongated, vascular pedicle. This tumor was resected without difficulty, and microscopic study showed the same fibrous tissue elements as in previous cases, with varying degrees of cellularity (Fig. 4B). It was interpreted as representing a typical benign pleural mesothelioma. There was immediate and complete relief of all her joint symptoms. By the time she was moved to the recovery room, all heat, redness, and swelling had disappeared from the affected joints, and the only evident residual was the digital clubbing. The latter persisted for approximately four months following removal of the tumor, but she was able to resume her work as a clerical typist immediately following convalescence from the thoracotomy. She continues to do well without joint symptoms and has no evidence of tumor recurrence eleven months postoperatively. B COMMENT It should be noted that in these patients the physical findings other than clubbing of the fingers and swollen, painful joints were those that would be expected in any case of intrathoracic tumor of similar size. None of them manifested any associated endocrine or metabolic derangements that could be detected. Also, there were no asbestos bodies or evidence of other foreign material responsible for inciting the tumor growth. The association of pathological changes in bones and joints with intrathoracic tumors and diseases has been noted frequently since it was first described independently by Bamberger [l] and Marie [9] in Although articular manifestations do occur in some cases of bronchogenic carcinoma and other tumors [131, they are not very common. It is therefore of considerable interest to note the frequency of these VOL. 2, NO. 5, SEPT.,
6 HUDSPETH findings with localized pleural mesotheliomas. If the tumors are truly benign, at least two-thirds or more of the patients will have this syndrome. Clagett et al. [3] were the first to call attention to this association, and two-thirds of his patients were affected. The fascinating questions are, Why do these patients have bone and joint manifestations? Why do the manifestations disappear immediately after removal of the tumor? Klemperer and Rabin [S] attributed them to lung compression with associated hypoxia; however, this is not adequate, since there is no correlation between tumor size and these manifestations-very small tumors produce the same picture [6]. In addition, massive compression from other tumors, thoracoplasty, etc., do not cause bone and joint manifestations. Also, blood gas studies were normal in two of the patients presented here. Meyer and Chaffee [lo] found hyaluronic acid produced by some malignant mesotheliomas, and this has been mentioned as a possible cause. However, malignant tumors do not produce this syndrome, and benign tumors have not been found to produce hyaluronic acid. This theory is further frustrated by the fact that disabling joint symptoms associated with bronchogenic carcinoma have disappeared following vagotomy [4], division of intercostal nerves [7], and even exploratory thoracotomy. Therefore, no logical explanation is available. Some humoral or neurohumoral mechanism is postulated. Although Cases 3 and 4 reported here are the first, to my knowledge, to be recognized preoperatively, with an increasing awareness of this tumor there undoubtedly will be many more patients available for careful preoperative study and more tumors for adequate bioassay. It may well be that this fascinating and unusual tumor holds significant clues which could prove of great benefit in the study of arthritis. SUMMARY Since 1957 four patients with localized benign pleural mesothelioma have been operated upon at the North Carolina Baptist Hospital. In every instance the patient sought medical aid because of disabling painful swelling and limitation of motion in joints of ankles, knees, elbows, hands, or spine. Three patients manifested clubbing. There were no symptoms referable to the chest, and treatment for arthritis had been given for varying periods of time prior to the chest roentgenogram. Each of the patients had a well-localized and pedunculated tumor which was technically very simple to remove and which on pathological study proved to be benign pleural mesothelioma. There was relief of all arthritic manifestations immediately following removal of the tumor. Follow-up observations from eleven months to seven years have revealed no tumor recurrence and no further joint symptoms. These cases 696 THE ANNALS OF THORACIC SURGERY
7 Mesotheliomas with Arthritis with their associated pathology are presented and their diagnostic and clinical features discussed. REFERENCES 1. Bamberger, quoted by Van Hazel Benoit, W. H., and Ackerman, L. V. Solitary pleural mesotheliomas. J. Thorac. Surg. 25:346, Clagett, 0. T., McDonald, J. R., and Schmidt, H. W. Localized fibrous mesothelioma of the pleura. J. Thorac. Sw.rg , Flavell, G. Reversal of pulmonary hypertrophic osteoarthropathy by vagotomy. Lancet 1:260, Gibbon, J. H., Jr. Surgery of the Chest. Philadelphia: Saunders, Heaney, J. P., Overton, R. C., and De Bakey, M. E. Benign localized pleural mesothelioma. J. Thorac. Surg. 34: 553, Holman, C. W. Osteoarthropathy in lung cancer: Disappearance after section of intercostal nerves. J. Thorac. Cardiov. Surg. 45:679, Klemperer, P., and Rabin, C. R. Primary neoplasms of the pleura: A report of five cases. Arch. Path. 11:385, Marie, P., quoted by Van Hazel [ Meyer, K., and Chaffee, E. Hyaluronic acid in the pleural fluid associated with a malignant tumor involving the pleura and peritoneum. J. Biol. Chem. 133:83, Stout, A. P., and Himandi, G. M. Solitary (localized) mesothelioma of the pleura. Ann. Surg. 133:50, Stout, A. P., and Murray, M. R. Localized pleural mesothelioma: Investigation of its characteristics and histogenesis by the method of tissue culture. Arch. Path. (Chicago) 34:951, Van Hazel, W. Joint manifestations associated with intrathoracic tumors. J. Thorac. Surg. 9:495, ERRATA For John H. Kennedy, M.D., Carl C. Enger, Jr., and Arthur G. Michel, B.A., A Subminiature Implantable Self-powered Cardiac Pacemaker: Experimental Observations, Volume 2, Number 4, July, Page 582, reference 4: For 10:73, 1964, read 10:373, Page 582, reference 5: For 9:48, 1965, read 11:148, Page 583, reference 11: For I.E.E.E. Trans. Med. Electronics read I.E.E.E. Trans. Biomed. Electronics; for 10:2, 1963, read 10:83, VOL. 2, NO. 5, SEPT.,
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