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Sclerosing mediastinitis with occlusion of pulmonary veins
Sclerosing mediastinitis with occlusion of pulmonary veins Manifestations and management A case of mediastinal fibrosis with occlusion of the right inferior and middle lobe pulmonary veins is described. The patient had severe hemoptysis, and the diagnosis was established with thoracotomy. Review of the literature emphasizes the lethal nature of this syndrome if untreated. Resection of the involved bronchopulmonary tissue, when feasible, offers good palliation, although the long-term prognosis is unpredictable.
T. E. Dye, M.D., Salim B. Saab, M.D., Carl H. Almond, M.D., and Linley Watson, M.D., Columbia, Mo.
HemoptysiS is a common clinical problem encountered by the thoracic surgeon. Its usual causes include bronchitis, bronchiectasis, pulmonary neoplasm, tuberculosis, and mitral stenosis. In eight to ten percent of patients the cause of bleeding goes undiscovered after diagnostic evaluation including bronchoscopic and bronchographic studies. If the hemoptysis is minimal and does not recur, further diagnostic studies are usually not warranted. In a patient with persistent hemoptysis, however, the evaluation must continue, even to include diagnostic thoractomy, until the cause of the bleeding is found. Mediastinal fibrosis with stenosis or occlusion of major pulmonary veins is an uncommon cause of severe hemoptysis. The purpose of this paper is to present a case in which thoracotomy was necessary for diagnosis. Only one other instance in which this condition was successfully diagnosed and managed has been found in the literature," although numerous autopsy cases have been reported. 3-8 A relevant review of the literature with comparison to the present case is also included in this report. From the Section of Thoracic and Cardiovascular Surgery and the Division of Cardiology, University of Missouri Medical Center, Columbia, Mo. Received for publication Dec. 6, 1976. Accepted for publication Feb. 7, 1977. Address for reprints: S. Saab, M.D., Assistant Professor of Surgery, Section of Thoracic and Cardiovascular Surgery, University of Missouri Medical Center, Columbia, Mo. 65201.
Case report A 32-year-old, obese, nonsmoking, black woman was referred to the University of Missouri Medical Center on Jan. 23, 1975, complaining of hemoptysis of 6 months' duration. She described paroxysms of cough, usually in the morning, which were accompanied by as much as one-half cup of bright red sputum. These episodes were associated with dyspnea, diaphoresis, and low-grade fever. She had no other cardiorespiratory symptoms. Findings on physical examination were unremarkable except for moderate obesity and a blood pressure of 185/95 mm. Hg. A roentgenogram of the chest was normal (Fig. I). Laboratory screen revealed a microcytic, hypochromic anemia with a hemoglobin value of 5.5 Gm. percent, a hematocrit value of 22 percent, a white blood cell count of 10,000 per cubic millimeters, and normal differential. Prothrombin time, partial thromboplastin time, and platelets were normal. A sickle cell preparation and tuberculin skin test were negative, although a mumps skin test was positive. Multiple sputum smears and cultures failed to grow mycobacteria, fungi, or other pathogens. Pulmonary function evaluation revealed a pH of 7.37, Pa o, of 79 mm. Hg, Paco, of 34 mm. Hg, and oxygen saturation of 95 percent, indicative of mild hypoxemia. Results of spirometry were normal. The electrocardiogram showed nonspecific ST-T changes. Normal studies included blood urea nitrogen, serum electrolytes and proteins, blood sugar and enzymes, and urinalysis. Bronchoscopic examination disclosed inflammatory changes in the bronchus intermedius with friability of the mucosa. Very little trauma by the bronchoscope resulted in profuse bleeding which required endobronchial epinephrine and tamponade for control. Bronchial biopsy showed inflammatory cells but no malignant disease. The lumen was slightly narrowed, but no bronchostenosis was appreciated by bronchographic study. Ventilation-perfusion scanning showed normal ventilation but poor perfusion in the right
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Fig. 1. Preoperative chest roentgenogram showing no active pulmonary disea se .
lower lung field. Pulmonary arteriograms showed obstruction of one basilar, segmental pulmonary arter y and absence of aborization of vessels to the right lower and middle lobes (Fig. 2). The venous phase of the arteriogram showed obstruction of the right inferior and middle lobe pulmonary veins, a finding that was not well appreciated initially (Fig . 3). After having a transfusion to increase the hemoglobin value to 10 Gm. percent, the patient was discharged on a regimen of iron, folate, and isoniazid to await the result of cultures. She was readmitted on March 17 and again on June 16, 1975. Bronchoscopic studies on both occasions precipitated the brisk bleeding notcd previousl y, even though hemopt ysis had become less frequent. During these admissions, it was noted that the hemoglobin value had stabilized at II Gm . percent. Aortograms showed no evidence of abnormal systemic vessels suppl ying the lungs . Still complaining of interm ittent hemopt ysis, the woman was readm itted to the University of Missouri Medical Center on July 20 , 1975. On July 22 , she underwent bronchoscopic examination followed immediately by right thoracotomy. At bronchoscopy, as on the previous occasions, copious bleeding from the right bronchus intermedius occurred with minimal bronchoscopic trauma. At right thoracotomy, striking neovascularity of pleural vessel s of the middle and lower lobes was noted , with a normal upper lobe. A stone-hard mass resembling a broncholith in consistenc y was palpated at the inferior border of the right hilum. However, the diagnosis of mediastinal fibrosis was made by multiple frozen section s, with no evidence of neoplasia . Bilobectomy was then carr ied out. Although the basilar pulmonary arterial sheaths were fibrotic, the arterial branches
Fig. 2. Arter ial phase of pulmonary arteriogram showing occlusion of a basilar segment artery and diminished vascularity in the middle and lower lobes of the right lung .
were dissected and severed without difficult y. Dense fibrous encasement obliterating the normal tissue planes required intrapericardial dissection of the inferior pulmonary vein, with inclusion of the left atrial wall within a noncrush ing clamp before division of the vein . The latter was found to be completely occluded by tile invading, hard, fibrous tissue. The middle lobe branch of the superior pulmonary vein was involved with the same process up to its junction with the upper lobe vein, which appeared normal. The most impressive microscopic findings consisted of dense fibrous tissue with many nests of acute and chronic inflammatory cells. This process involved and totally replaced the wall of pulmonary veins, which also showed marked intimal proliferation. The process surrounded and infiltrated the adjacent bronchus . Although large pulmonary arter y branches showed minimal intimal hyperpl asia, small pulmonary artery branches showed marked intimal hyperplasia. The pulmonary parenchyma showed focal atelectasis, interstitial fibrosis, and accumula tion of hemosiderin-laden macrophages. Fibrous tissue also infiltrated that portion of the left atrial wall which was included with the resected pulmonary vein. Postoperatively, the patient's course was uncomplicated except for a benign apical space which resolved spontaneously (Fig. 4) . Sixteen month s after operation , she is free of hemopt ysis and feels well except for mild exertional dyspnea.
Discussion Mediastinal fibrosis is an obliterative "inflammatory fibrosist'f of uncertain and perhaps multiple causes,
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Fig. 3. Venous phase of pulmonary arteriogram shows complete obstruction of inferior pulmonary vein extending to its junction with the left atrium (lower arrow). Obstruction of middle lobe vein is also shown (upper arrow).
Fig. 4. Postoperative chest x-ray film.
capable of involving any organ in the mediastinum. At one time, tuberculosis and syphilis were the most frequently suspected causes.v- 9-11 Other infectious agents, such as Histoplasma- 12 and Nocardia," have been implicated. Most often, however, a cause is never discovered, as in our patient. To emphasize its inflammatory nature, idiopathic mediastinal fibrosis has also been called "sclerosing mediastinitis'V: 5. 11 and is considered one of a group of related fibrous diseases which include retroperitoneal fibrosis,": 5. 11. 13 sclerosing cholangitis.w" Reidel's struma, 13. 15. 17 orbital pseudotumor, 13 ligneous perityphlitis.v 10 and sclerosing cervicitis. 18 These diseases, all characterized by a fibrous tissue overgrowth with a similar histologic picture, have been found in patients either singly or in various combinations. Their cause remains obscure, although the drug methysergide has been implicated in some cases of retroperitoneal fibrosis and sclerosing cholangitis. 19. 20 Genetic factors have been considered because of a report of consanguinous siblings with combinations of these diseases by Comings and his associates.P who suggested the general term "rnultifocal fibrosclerosis" for the whole group. Hypersensitivity reaction, a collagen disease, an autoimmune process, and even neoplasms have also been proposed as causative factors. 2
Mediastinal fibrosis can constrict or obliterate any structure located in the mediastinum. It seems to have no sex preference and is seen most frequently between the second and fifth decades of life. Superior vena caval obstruction is the most commonly reported clinical manifestation," 9. 10. 12 but involvement of the esophagus;" trachea and major bronchi, 2 pulmonary artery;" and pulmonary veins has been reported. Although it has been stated that the process does not invade the pericardium," involvement of coronary arteries'" has been seen, and, in our case, cardiac muscle included in the pathological specimen was involved. Of the protean manifestations!' of sclerosing mediastinitis, pulmonary vein obstruction is perhaps the most insidious. The symptoms of cough, hemoptysis, and dyspnea caused by the disorder are common to many chest diseases. Mitral stenosis and cardiac tumor are diagnoses that have been considered in patients with pulmonary vein obstruction, even after cardiac catheterization.": 8 Indeed, the possibility of an atrial myxoma was entertained in our patient. Most patients with the disease have died from either intractable heart failure 3 - 8 or tracheobronchial hemorrhage. 3. 5 In all reported cases there was considerable hemoptysis.":" Also, bronchoscopic examinations seem to aggravate the endobronchial hemorrhage, as was noted
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on three separate occasions in our patient. Hemorrhage initiated by the bronchoscope resulted in the death of one patient." The hemorrhage could be either intraalveolar from pulmonary hypertension" or intrabronchial from increased bronchial collateral circulation. 24, 25 The latter probably accounts for the bleeding from endoscopic trauma. Venous collateral circulation after ligation of the pulmonary veins has been well described. 23. 24 The fact that most instances of mediastinal fibrosis with occlusion of pulmonary veins have been reported from autopsy studies indicates that clinical diagnosis of this disease is rarely made. In our patient, the pulmonary arteriogram was very suggestive and should have been most helpful in establishing the correct diagnosis. Abnormalities in both the arterial and venous phases were present. The cause of the arterial lesion could be reflex medial hypertrophy rather than primary involvement by the fibrous process. 7 In our patient, however, the pulmonary arterial lesion consisted of intimal hyperplasia. Kittredge and Nash" have stressed the importance of the venous phase of the pulmonary arteriogram in diagnosis, but they saw dilation of the pulmonary vein proximal to the left atrium rather than the complete occlusion present in our patient. Nonspecific radiographic signs of the disease include pulmonary consolidation or atelectasis.s increased peripheral vascular markings, and increased hilar size." At thoracotomy, nodular mass(es) is characteristically described at the pulmonary hilum, which is woody or stone hard in consistency, 2 raising the possibility of malignant disease or broncholithiasis in the differential diagnosis. Management of mediastinal fibrosis is uncertain. 9 Steroid therapy is beneficial in certain fibrosclerotic disorders, most notably sclerosing cholangitis and retroperitoneal fibrosis. 16. 18. 26 Steroids have also been advocated in sclerosing mediastinitis." 5 In one patient whose condition had improved, cervical and abdominal biopsy specimens indicated sclerosing fibrosis and a pretreatment mediastinal mass which regressed after institution of steroids." Diagnosis from the biopsy specimen is important, not only for documentation of the results of therapy, but also to rule out certain malignant disorders prior to treatment, particularly the desmoplastic response caused by Hodgkin's disease, reticulum cell sarcoma, and carcinoid tumors. 2, 5, 11 Surgical resection constitutes the mainstay of therapy in the mediastinal form of the disease." Patients with tracheobronchial constriction or severe hemoptysis require some form of immediate palliation. Like steroid therapy, however, long-term beneficial results of operation are not documented because of the few cases seen.
Thoracic and Cardiovascular Surgery
Although progressive obstruction may occur owing to the invasive nature of the inflammatory fibrous tissue reaction," it is not known whether the disease invariably progresses relentlessly to involve other organs in the mediastinum or whether it may eventually be arrested. Therefore, our patient will receive lifetime follow-up. In conclusion, the following may be emphasized in relation to fibrosing mediastinitis: 1. Although the specific cause is still obscure, the histopathological changes are simple and clear, consisting of an invasive, inflammatory, dense, fibrous tissue process that infiltrates and thereby causes constriction of the tubular mediastinal structures. This differentiates it from simple fibrosis and scarring which causes constriction by extrinsic compression only. 2. The clinical manifestations depend on the geographic location of the disease; however, it is reasonable to expect that the venous structures (e.g., superior vena cava and pulmonary veins) may be compromised earlier, because of their collapsible thin wall and low intraluminal pressure, followed by pulmonary arteries and the tracheobronchial tree. This probably explains why the superior vena cava syndrome and hemoptysis are the more common symptoms of the disease. 3. Although the constrictive sequelae of the disease may be demonstrated by a series of studies including bronchoscopy, bronchography, and angiography, the diagnosis is usually established by histopathological changes present in excised tissue at thoracotomy. Therefore, the evaluation of recurrent hemoptysis should continue until the cause is unveiled, even if this may require a thoracotomy. A thorough search of multiple frozen sections as well as permanent sections of the resected specimen will rule out a neoplastic focus. 4. Two modalities of treatment exist at present: surgical resection of involved bronchopulmonary tissue for localized disease and steroid therapy for advanced disease or for cases in which resection is not feasible. It is not clear whether steroids should be given in conjunction with surgical resection as a prophylactic measure against further progression of the disease. 5. In view of the uncertain and potentially grave prognosis of this entity, lifelong follow-up of patients is advised. REFERENCES Daly, J. F., Boyd, A., and Spencer, F. C.: Endoscopy: Bronchoscopy and Esophagoscopy, Chap. 2, Gibbon's Surgery of the Chest, ed. 3, Philadelphia, 1976, W. A. Saunders Company. 2 Dozois, R. R., Bumatz, P. E., Woolner, L. B., and
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Andersen, H. A.: Sclerosing Mediastinitis Involving Major Bronchi, Mayo Clin. Proc. 43: 557, 1968. Bindelglass, I. L., and Trubowitz, S.: Pulmonary Vein Obstruction: An Uncommon Sequel to Chronic Fibrous Mediastinitis, Ann. Intern. Med. 43: 876, 1958. Leech, T. R., Meckstroth, C. V., and Klassen, K. P.: Exploratory Thoracotomy in Chronic Lymphadenitis of the Mediastinum, Arch. Surg. 71: 383, 1955. Kittredge, R. D., and Nash, A. D.: The Many Facets of Sclerosing Fibrosis, Am. J. Roentgeno!. Radium Ther. Nuc!. Med. 122: 288, 1974. Erganian, J., and Wade, L. J.: Chronic Fibrous Mediastinitis With Obstruction of the Superior Vena Cava, J. THoRAc. SVRG. 12: 275, 1943. Edwards, 1. E., and Burchell, H. B.: Multilobar Pulmonary Venous Obstruction With Pulmonary Hypertension, Arch. Intern. Med. 87: 372, 1951. Davis, F. W., and Andrus, E. C.: Mitral Stenosis in Fascimile, N. Eng!. J. Med. 251: 299, 1954. Barrett, N. R.: Idiopathic Mediastinal Fibrosis, Br. 1. Surg. 46: 207, 1958. Hache, L., Woolner, L. B., and Bernatz, P. E.: Idiopathic Fibrous Mediastinitis, Chest 41: 9, 1962. Buckberg, G. D., Dilley, R. B., and Longmire, W. P., Jr.: The Protean Manifestations of Sclerosing Fibrosis, Surg. Gyneco!. Obstet. 123: 729, 1966. Salyer, 1. M., Harrison, H. N., Winn, D. S., and Taylor, R. R.: Chronic Fibrosis Mediastinitis and Superior Vena Caval Obstruction Due to Histoplasmosis, Chest 135: 364, 1959. Comings, D. E., Skubi, K. B., Van Eyes, J., and Motulsky, A. G.: Familial Multifocal Fibrosclerosis, Ann. Intern. Med. 66: 884, 1967. Bartholomew, L. G., Cain, J. C., Woolner, L. B., Utz, D. C.; and Ferris, D.O.: Sclerosing Cholangitis, N. Eng!. 1. Med. 269: 8, 1963. Wenger, 1., Gingrich, G. W., and Mendeloff, 1.: Sclerosing Cholangitis: A Manifestation of Systemic Disease, Arch. Intern. Med. 116: 509, 1965.
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16 Cutler, B., and Donaldson, G. A.: Primary Sclerosing Cholangitis and Obliterative Cholangitis. Am. J. Surg. 117: 502, 1969. 17 Gleeson, M. H., Taylor, S., and Dowling, R. H.: Multifocal Fibroslerosis, Proc. R. Soc. Med. 63: 1309, 1970. 18 Rice, D. H., Batsakis, J. G., and Coulthard, S. W.: Sclerosing Cervicitis: Homologue of Sclerosing Retroperitonitis and Mediastinitis, Arch. Surg. 110: 120, 1975. 19 Utz, D. c., Rooke, E. D., Spittell, 1. A., Jr., and Bartholomew, L. G.: Retroperitoneal Fibrosis in Patients Taking Methysergide, 1. A. M. A. 192: III, 1965. 20 Graham, J. R., Suby, H. I., LeCompte, P. R., and Sadowsky, N. L.: Fibrotic Disorders Associated With Methysergide Therapy for Headache, N. Eng!. J. Med. 274: 359, 1966. 21 Marshall, R. J., Edmundowicz, A. c., and Andrews, C. E.: Chronic Obstruction of the Superior Vena Cava Due to Histoplasmosis: A Hemodynamic and Angiographic Correlation, Circulation 29: 604, 1964. 22 Reed, W. G., and Stinely, R. W.: Massive Periaortic and Periarterial Fibrosis: Report of a Case, N. Eng!. J. Med. 261: 320, 1959. 23 Hurwitz, A., Calabresi, M., Cooke, R. W., and Liebow, A. A.: An Experimental Study of the Venous Colateral Circulation of the Lung. I. Anatomic Observation, Am. J. Patho!. 30: 1085, 1954. 24 Hurwitz, A., Calabresi, M., Cooke, R. W., and Liebow, A. A.: An Experimental Study of the Venous Colateral Circulation of the Lung. II. Functional Observations, J. THORAC. SURG. 28: 241, 1954. 25 Friedberg, S. A.: Hemoptysis Secondary to Chronic Mediastinal Venous Obstruction, Ann. Otolaryngo!. 57: 897, 1948. 26 Morandi, L. T., and Grobe, T. J.: Retroperitoneal Fibrosis, Arch. Intern. Med. 128: 295, 1971.
T. E. Dye, M.D., Salim B. Saab, M.D., Carl H. Almond, M.D., and Linley Watson, M.D., Columbia, Mo.
HemoptysiS is a common clinical problem encountered by the thoracic surgeon. Its usual causes include bronchitis, bronchiectasis, pulmonary neoplasm, tuberculosis, and mitral stenosis. In eight to ten percent of patients the cause of bleeding goes undiscovered after diagnostic evaluation including bronchoscopic and bronchographic studies. If the hemoptysis is minimal and does not recur, further diagnostic studies are usually not warranted. In a patient with persistent hemoptysis, however, the evaluation must continue, even to include diagnostic thoractomy, until the cause of the bleeding is found. Mediastinal fibrosis with stenosis or occlusion of major pulmonary veins is an uncommon cause of severe hemoptysis. The purpose of this paper is to present a case in which thoracotomy was necessary for diagnosis. Only one other instance in which this condition was successfully diagnosed and managed has been found in the literature," although numerous autopsy cases have been reported. 3-8 A relevant review of the literature with comparison to the present case is also included in this report. From the Section of Thoracic and Cardiovascular Surgery and the Division of Cardiology, University of Missouri Medical Center, Columbia, Mo. Received for publication Dec. 6, 1976. Accepted for publication Feb. 7, 1977. Address for reprints: S. Saab, M.D., Assistant Professor of Surgery, Section of Thoracic and Cardiovascular Surgery, University of Missouri Medical Center, Columbia, Mo. 65201.
Case report A 32-year-old, obese, nonsmoking, black woman was referred to the University of Missouri Medical Center on Jan. 23, 1975, complaining of hemoptysis of 6 months' duration. She described paroxysms of cough, usually in the morning, which were accompanied by as much as one-half cup of bright red sputum. These episodes were associated with dyspnea, diaphoresis, and low-grade fever. She had no other cardiorespiratory symptoms. Findings on physical examination were unremarkable except for moderate obesity and a blood pressure of 185/95 mm. Hg. A roentgenogram of the chest was normal (Fig. I). Laboratory screen revealed a microcytic, hypochromic anemia with a hemoglobin value of 5.5 Gm. percent, a hematocrit value of 22 percent, a white blood cell count of 10,000 per cubic millimeters, and normal differential. Prothrombin time, partial thromboplastin time, and platelets were normal. A sickle cell preparation and tuberculin skin test were negative, although a mumps skin test was positive. Multiple sputum smears and cultures failed to grow mycobacteria, fungi, or other pathogens. Pulmonary function evaluation revealed a pH of 7.37, Pa o, of 79 mm. Hg, Paco, of 34 mm. Hg, and oxygen saturation of 95 percent, indicative of mild hypoxemia. Results of spirometry were normal. The electrocardiogram showed nonspecific ST-T changes. Normal studies included blood urea nitrogen, serum electrolytes and proteins, blood sugar and enzymes, and urinalysis. Bronchoscopic examination disclosed inflammatory changes in the bronchus intermedius with friability of the mucosa. Very little trauma by the bronchoscope resulted in profuse bleeding which required endobronchial epinephrine and tamponade for control. Bronchial biopsy showed inflammatory cells but no malignant disease. The lumen was slightly narrowed, but no bronchostenosis was appreciated by bronchographic study. Ventilation-perfusion scanning showed normal ventilation but poor perfusion in the right
137
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Dye et al.
7 20 75
Fig. 1. Preoperative chest roentgenogram showing no active pulmonary disea se .
lower lung field. Pulmonary arteriograms showed obstruction of one basilar, segmental pulmonary arter y and absence of aborization of vessels to the right lower and middle lobes (Fig. 2). The venous phase of the arteriogram showed obstruction of the right inferior and middle lobe pulmonary veins, a finding that was not well appreciated initially (Fig . 3). After having a transfusion to increase the hemoglobin value to 10 Gm. percent, the patient was discharged on a regimen of iron, folate, and isoniazid to await the result of cultures. She was readmitted on March 17 and again on June 16, 1975. Bronchoscopic studies on both occasions precipitated the brisk bleeding notcd previousl y, even though hemopt ysis had become less frequent. During these admissions, it was noted that the hemoglobin value had stabilized at II Gm . percent. Aortograms showed no evidence of abnormal systemic vessels suppl ying the lungs . Still complaining of interm ittent hemopt ysis, the woman was readm itted to the University of Missouri Medical Center on July 20 , 1975. On July 22 , she underwent bronchoscopic examination followed immediately by right thoracotomy. At bronchoscopy, as on the previous occasions, copious bleeding from the right bronchus intermedius occurred with minimal bronchoscopic trauma. At right thoracotomy, striking neovascularity of pleural vessel s of the middle and lower lobes was noted , with a normal upper lobe. A stone-hard mass resembling a broncholith in consistenc y was palpated at the inferior border of the right hilum. However, the diagnosis of mediastinal fibrosis was made by multiple frozen section s, with no evidence of neoplasia . Bilobectomy was then carr ied out. Although the basilar pulmonary arterial sheaths were fibrotic, the arterial branches
Fig. 2. Arter ial phase of pulmonary arteriogram showing occlusion of a basilar segment artery and diminished vascularity in the middle and lower lobes of the right lung .
were dissected and severed without difficult y. Dense fibrous encasement obliterating the normal tissue planes required intrapericardial dissection of the inferior pulmonary vein, with inclusion of the left atrial wall within a noncrush ing clamp before division of the vein . The latter was found to be completely occluded by tile invading, hard, fibrous tissue. The middle lobe branch of the superior pulmonary vein was involved with the same process up to its junction with the upper lobe vein, which appeared normal. The most impressive microscopic findings consisted of dense fibrous tissue with many nests of acute and chronic inflammatory cells. This process involved and totally replaced the wall of pulmonary veins, which also showed marked intimal proliferation. The process surrounded and infiltrated the adjacent bronchus . Although large pulmonary arter y branches showed minimal intimal hyperpl asia, small pulmonary artery branches showed marked intimal hyperplasia. The pulmonary parenchyma showed focal atelectasis, interstitial fibrosis, and accumula tion of hemosiderin-laden macrophages. Fibrous tissue also infiltrated that portion of the left atrial wall which was included with the resected pulmonary vein. Postoperatively, the patient's course was uncomplicated except for a benign apical space which resolved spontaneously (Fig. 4) . Sixteen month s after operation , she is free of hemopt ysis and feels well except for mild exertional dyspnea.
Discussion Mediastinal fibrosis is an obliterative "inflammatory fibrosist'f of uncertain and perhaps multiple causes,
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Fig. 3. Venous phase of pulmonary arteriogram shows complete obstruction of inferior pulmonary vein extending to its junction with the left atrium (lower arrow). Obstruction of middle lobe vein is also shown (upper arrow).
Fig. 4. Postoperative chest x-ray film.
capable of involving any organ in the mediastinum. At one time, tuberculosis and syphilis were the most frequently suspected causes.v- 9-11 Other infectious agents, such as Histoplasma- 12 and Nocardia," have been implicated. Most often, however, a cause is never discovered, as in our patient. To emphasize its inflammatory nature, idiopathic mediastinal fibrosis has also been called "sclerosing mediastinitis'V: 5. 11 and is considered one of a group of related fibrous diseases which include retroperitoneal fibrosis,": 5. 11. 13 sclerosing cholangitis.w" Reidel's struma, 13. 15. 17 orbital pseudotumor, 13 ligneous perityphlitis.v 10 and sclerosing cervicitis. 18 These diseases, all characterized by a fibrous tissue overgrowth with a similar histologic picture, have been found in patients either singly or in various combinations. Their cause remains obscure, although the drug methysergide has been implicated in some cases of retroperitoneal fibrosis and sclerosing cholangitis. 19. 20 Genetic factors have been considered because of a report of consanguinous siblings with combinations of these diseases by Comings and his associates.P who suggested the general term "rnultifocal fibrosclerosis" for the whole group. Hypersensitivity reaction, a collagen disease, an autoimmune process, and even neoplasms have also been proposed as causative factors. 2
Mediastinal fibrosis can constrict or obliterate any structure located in the mediastinum. It seems to have no sex preference and is seen most frequently between the second and fifth decades of life. Superior vena caval obstruction is the most commonly reported clinical manifestation," 9. 10. 12 but involvement of the esophagus;" trachea and major bronchi, 2 pulmonary artery;" and pulmonary veins has been reported. Although it has been stated that the process does not invade the pericardium," involvement of coronary arteries'" has been seen, and, in our case, cardiac muscle included in the pathological specimen was involved. Of the protean manifestations!' of sclerosing mediastinitis, pulmonary vein obstruction is perhaps the most insidious. The symptoms of cough, hemoptysis, and dyspnea caused by the disorder are common to many chest diseases. Mitral stenosis and cardiac tumor are diagnoses that have been considered in patients with pulmonary vein obstruction, even after cardiac catheterization.": 8 Indeed, the possibility of an atrial myxoma was entertained in our patient. Most patients with the disease have died from either intractable heart failure 3 - 8 or tracheobronchial hemorrhage. 3. 5 In all reported cases there was considerable hemoptysis.":" Also, bronchoscopic examinations seem to aggravate the endobronchial hemorrhage, as was noted
The Journal of
14 0
Dye et al,
on three separate occasions in our patient. Hemorrhage initiated by the bronchoscope resulted in the death of one patient." The hemorrhage could be either intraalveolar from pulmonary hypertension" or intrabronchial from increased bronchial collateral circulation. 24, 25 The latter probably accounts for the bleeding from endoscopic trauma. Venous collateral circulation after ligation of the pulmonary veins has been well described. 23. 24 The fact that most instances of mediastinal fibrosis with occlusion of pulmonary veins have been reported from autopsy studies indicates that clinical diagnosis of this disease is rarely made. In our patient, the pulmonary arteriogram was very suggestive and should have been most helpful in establishing the correct diagnosis. Abnormalities in both the arterial and venous phases were present. The cause of the arterial lesion could be reflex medial hypertrophy rather than primary involvement by the fibrous process. 7 In our patient, however, the pulmonary arterial lesion consisted of intimal hyperplasia. Kittredge and Nash" have stressed the importance of the venous phase of the pulmonary arteriogram in diagnosis, but they saw dilation of the pulmonary vein proximal to the left atrium rather than the complete occlusion present in our patient. Nonspecific radiographic signs of the disease include pulmonary consolidation or atelectasis.s increased peripheral vascular markings, and increased hilar size." At thoracotomy, nodular mass(es) is characteristically described at the pulmonary hilum, which is woody or stone hard in consistency, 2 raising the possibility of malignant disease or broncholithiasis in the differential diagnosis. Management of mediastinal fibrosis is uncertain. 9 Steroid therapy is beneficial in certain fibrosclerotic disorders, most notably sclerosing cholangitis and retroperitoneal fibrosis. 16. 18. 26 Steroids have also been advocated in sclerosing mediastinitis." 5 In one patient whose condition had improved, cervical and abdominal biopsy specimens indicated sclerosing fibrosis and a pretreatment mediastinal mass which regressed after institution of steroids." Diagnosis from the biopsy specimen is important, not only for documentation of the results of therapy, but also to rule out certain malignant disorders prior to treatment, particularly the desmoplastic response caused by Hodgkin's disease, reticulum cell sarcoma, and carcinoid tumors. 2, 5, 11 Surgical resection constitutes the mainstay of therapy in the mediastinal form of the disease." Patients with tracheobronchial constriction or severe hemoptysis require some form of immediate palliation. Like steroid therapy, however, long-term beneficial results of operation are not documented because of the few cases seen.
Thoracic and Cardiovascular Surgery
Although progressive obstruction may occur owing to the invasive nature of the inflammatory fibrous tissue reaction," it is not known whether the disease invariably progresses relentlessly to involve other organs in the mediastinum or whether it may eventually be arrested. Therefore, our patient will receive lifetime follow-up. In conclusion, the following may be emphasized in relation to fibrosing mediastinitis: 1. Although the specific cause is still obscure, the histopathological changes are simple and clear, consisting of an invasive, inflammatory, dense, fibrous tissue process that infiltrates and thereby causes constriction of the tubular mediastinal structures. This differentiates it from simple fibrosis and scarring which causes constriction by extrinsic compression only. 2. The clinical manifestations depend on the geographic location of the disease; however, it is reasonable to expect that the venous structures (e.g., superior vena cava and pulmonary veins) may be compromised earlier, because of their collapsible thin wall and low intraluminal pressure, followed by pulmonary arteries and the tracheobronchial tree. This probably explains why the superior vena cava syndrome and hemoptysis are the more common symptoms of the disease. 3. Although the constrictive sequelae of the disease may be demonstrated by a series of studies including bronchoscopy, bronchography, and angiography, the diagnosis is usually established by histopathological changes present in excised tissue at thoracotomy. Therefore, the evaluation of recurrent hemoptysis should continue until the cause is unveiled, even if this may require a thoracotomy. A thorough search of multiple frozen sections as well as permanent sections of the resected specimen will rule out a neoplastic focus. 4. Two modalities of treatment exist at present: surgical resection of involved bronchopulmonary tissue for localized disease and steroid therapy for advanced disease or for cases in which resection is not feasible. It is not clear whether steroids should be given in conjunction with surgical resection as a prophylactic measure against further progression of the disease. 5. In view of the uncertain and potentially grave prognosis of this entity, lifelong follow-up of patients is advised. REFERENCES Daly, J. F., Boyd, A., and Spencer, F. C.: Endoscopy: Bronchoscopy and Esophagoscopy, Chap. 2, Gibbon's Surgery of the Chest, ed. 3, Philadelphia, 1976, W. A. Saunders Company. 2 Dozois, R. R., Bumatz, P. E., Woolner, L. B., and
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