Swyer-James (MacLeod) Syndrome With Placental Transmogrification of the Lung: A Case Report and Review of the Literature

Swyer-James (MacLeod) syndrome is an acquired form of unilateral hyperlucency of the lung and is characterized by the development of severe emphysema, bronchiectasis, and/or bronchiolitis obliterans. It may develop as a complication of repeated episodes of pulmonary infection resulting in bronchiolitis obliterans and obstruction of small airways. Most patients with Swyer-James (MacLeod) syndrome can be managed clinically, and the pathologic features of the syndrome have been described in only a few reports. Placental transmogrification of the lung is a rare histopathologic finding that has been described in patients with severe emphysema associated with cigarette smoking, congenital bullous emphysema, and fibrochondromatous hamartomas of the lung and is characterized by the development of peculiar structures in the pulmonary parenchyma that resemble placental villi. To our knowledge, placental transmogrification of the lung has not been previously described in patients with Swyer-James (MacLeod) syndrome. We encountered a 32- year-old man with a history of childhood asthma who presented with progressively severe exertional dyspnea and had unilateral right lung hyperlucency. The patient underwent a right pneumonectomy. Examination of the lung revealed severe mixed centriacinar- panacinar emphysema in all lobes, bullous emphysema in the upper lobe, bronchiectases, mild interstitial pneumonia with fibrosis, and placental transmogrification of the pulmonary parenchyma of all 3 lobes. Here, we review the pathology of Swyer-James (MacLeod) syndrome and the possible pathogenesis of villous-like changes in the lung tissues.

(Arch Pathol Lab Med. 2005;129:686-689)

In 1952, Swyer and James published a report on a 6-year-old child with unilateral pulmonary emphysema that was treated with pneumonectomy.1 The patient had a clinical history of recurrent bronchopneumonia and bronchitis that affected only the right lung. Chest radiographs revealed relative transradiancy of the right lung field with a significant decrease in vascular markings. The resected lung had multiple cystic spaces, emphysema, chronic inflammatory changes, and unremarkable bronchi. The authors suggested that the condition was probably acquired as a result of recurrent episodes of bronchopneumonia and bronchitis. In 1953, MacLeod reported the clinical and radiologic features of similar abnormal transradiancy of one lung in 9 adult patients ranging in age from 18 to 41 years.2 None of these patients had valvelike mucosal flaps in the bronchial mucosa, as previously described in children with congenital lobar emphysema, or exhibited the abnormal vascular changes of patients with congenital hypoplasia of the lung.

Swyer-James syndrome, synonymous with MacLeod syndrome, is currently recognized as one of several causes of unilateral translucent lung3-6 and has been reported in more than 100 patients. The syndrome is thought to be secondary to bronchiolitis obliterans acquired in infancy, resulting in obstruction of small airways and secondary emphysema. Patients with Swyer-James (MacLeod) syndrome may be asymptomatic at diagnosis but usually present with a history of recurrent episodes of pulmonary infection with onset early in life. Patients usually have dyspnea on exertion, hemoptysis, and/or chronic productive cough, and they may develop severe respiratory impairment that requires pneumonectomy. Imaging studies reveal the presence of unilateral lung hyperlucency and hypoplastic hilar vessels. The condition must be distinguished from absence or occlusion of the pulmonary artery, partial obstruction of the main bronchus, and congenital lobar emphysema.

Placental transmogrification or placentoid bullous lesion of the lung is an unusual condition in which the alveoli develop a peculiar villous configuration that resembles (at low microscopic magnification) placental villi.6 The villous appearance of these pulmonary tissues probably results from the development of edema and fibrosis in the residual strands of alveolar tissue present in the enlarged airspaces of severe emphysema. Placental transmogrification of the lung has been described in patients with severe emphysema induced by cigarette smoking, congenital giant bullous emphysema, and fibrochondromatous hamartomas of the lung.7-13 Hochholzer and associates10 reported an unusual patient with pulmonary lipomatosis as a variant of placental transmogrification. To our knowledge, this unusual villous change of the lung has not been reported in patients with the Swyer-James (MacLeod) syndrome. Here, we report a patient with Swyer-James (MacLeod) syndrome who had placental transmogrification of the lung as revealed by microscopic examination of the resected lung.

Pre- and Postoperative Pulmonary Function Test Results Following Right Pneumonectomy

REPORT OF A CASE

A 32-year-old nonsmoking man with a life-long history of mild asthma presented to the Cedars-Sinai Medical Center Lung Center with progressive dyspnea on exertion, back pain, and a productive cough. The patient had been previously able to walk briskly 1 to 2 miles twice a week, but his exercise tolerance diminished over several months with a significant increase in dyspnea. At initial evaluation, he denied fever, chills, weight loss, anorexia, and significant sputum production but complained of severe dyspnea on exertion. Physical examination revealed a midline trachea with no cervical or supracervical lymphadenopathy. Auscultation revealed scattered rales in the right chest with decreased breath sounds at the right apex. The left hemithorax was clear throughout, and asymmetric expansion of the chest was noted. The remainder of his physical examination was unremarkable. Laboratory data included a white blood cell count of 7700/l, red blood cell count of 3.2 10^sup 6^/L, hemoglobin of 10.0 g/dL, and hematocrit of 29.2%. The differential count was as follows: polymorphonuclear leukocytes, 76%; lymphocytes, 11%; monocytes, 9%; and eosinophils, 4%. Aerobic bacterial culture yielded coagulase-negative Staphylococcus sp, but anaerobic and fungal culture results were negative.

Pulmonary function tests revealed an obstructive pattern with significant air trapping and evidence of disease of the small airways (Table). High-resolution chest computed tomography scans of the chest (Figure 1) revealed extensive emphysematous changes and bullae in the right hemithorax. The large right apical bullae displaced the anterior junctional line toward the left hemithorax by 8.5 cm. There was also a shift of the mediastinum to the left. Areas of consolidated lung with air bronchograms were present in the basal segments of the right lower lobe suggestive of recent pneumonia. A quantitative ventilation/perfusion scan revealed severely decreased tracer activity in the right lung, which received only 16% of the total lung perfusion.

These results suggested that the increasing dyspnea was secondary to compression of a normal left lung by a markedly hyperinflated and essentially nonfunctional right lung. The patient underwent a right pneumonectomy to relieve the mechanical cause of his dyspnea and to obtain a definitive diagnosis of the underlying pathology. At the time of surgery, there were a few scattered adhesions throughout the right hemithorax. The right lung appeared almost 3 times normal size. Large bullae were opened to decompress the right lung and to allow room to proceed with the operation. The patient had an uneventful postoperative course and was discharged on the 5th postoperative day.

The resected right lung weighed 1460 g and had severe, diffuse emphysema throughout with bullous emphysema in the right upper lobe (Figures 2 and 3). Emphysematous spaces ranged in largest diameter from 0.2 to 6.0 cm. Cylindrical bronchiectasis with peribronchial fibrosis was observed in the right upper lobe, with bronchi up to 4.0 mm in diameter extending close to the pleura. The pulmonary vessels were grossly unremarkable. Microscopically, the lung had severe mixed bullous, panacinar, and centriacinar emphysema, bronchiectases, and patchy areas of nonspecific interstitial fibrosis (Figures 4 through 6). In some of the sections taken from all lobes, the severely emphysematous lung had foci of placental transmogrification with rare areas of adipose tissue in the villous septal structures (Figure 6). The villous structures present within the emphysematous lung tissue exhibited edema, neovascularization, and patchy chronic inflammation (Figures 5 and 6). Patchy areas of interstitial fibrosis were more prominent in a subpleural and peribronchial distribution and were focally associated with osseous metaplasia. The lung also showed patchy chronic interstitial inflammation with multiple cholesterol granulomas and marked edema of the alveolar septa. No obliterative bronchiolitis was seen. Trichrome stains confirmed the presence of patchy areas of interstitial fibrosis. Result of an immunohistochemical stain for HMB-45 was negative. Tissues stained with acid fast bacteria stain and Gomori methenamine silver stain were negative for microorganisms.

PATHOLOGIC FINDINGS

To our knowledge, the pathologic features of the lung in patients with Swyer-James (MacLeod) syndrome have been previously d\escribed in only 4 other cases, none of which exhibited placental transmogrification of the pulmonary parenchyma.1,5,6,14,15 In addition to the original case described in 1953 by Swyer and James, the case reports by Morita et al5 and Koyama et al6 included a description of the pathologic changes found in lung resection specimens. These changes included emphysema, cystic cavities lined by ciliated columnar epithelium probably representing saccular bronchiectasis, cylindrical bronchiectasis, interstitial chronic inflammatory changes, lymphadenoid nodules probably representing hyperplasia of bronchusassociated lymphoid tissue, widespread obliteration of the pulmonary capillary bed as a result of emphysema, hypertrophy of the pulmonary artery probably resulting from pulmonary hypertension changes secondary to emphysema, bronchitis and bronchiolitis, and peribronchial fibrosis and smooth muscle proliferation. The patient described by Morita et al5 also exhibited severe stenosis of the bronchus intermedius. The features in the present case emphasize that the emphysema in Swyer-James (McLeod) syndrome can be so severe as to result in placental transmogrification of the lung, a change typically restricted to severe bullous emphysema.

In the present case, small numbers of adipose cells were found in the villous structures. In 1997, Hochholzer et al10 reported the presence of “strikingly papillary structures composed almost exclusively of mature adipose tissue with small collections of inflammatory cells” in a patient with severe emphysema. The diagnosis of pulmonary lipomatosis as a variant of placental transmogrification in the setting of pulmonary emphysema was suggested.

Figure 1. Chest computed tomography scan revealing right lung hyperlucency due to severe bullous and panacinar emphysema that displaces the mediastinum to the left side and compresses the contralateral lung.

Figure 2. Photograph of the right upper lung lobe revealing severe emphysema with bullous disease, bronchiectasis, and peribronchial fibrosis.

Figure 3. Photograph of the right lower lung lobe revealing diffuse changes of panacinar emphysema.

Figure 4. Low-power micrograph of the right upper lung lobe revealing emphysema and villous structures of placental transmogrification (hematoxylin-eosin, original magnification 40).

Figure 5. Intrapulmonary villous structures within the right lower lung lobe with variable chronic inflammation admixed with emphysematous lung tissue (hematoxylin-eosin, original magnification 100).

Figure 6. High magnification of a villous structure with edema, neovascularization, mild chronic inflammation, and focal peripheral adipocytes (hematoxylin-eosin, original magnification 200).

The pathogenesis of placental transmogrification or placentoid bullous lesions of the lung is unknown. It has been associated with severe emphysema induced by cigarette smoking, giant bullous emphysema of the lung (a congenital condition that usually affects a single lung lobe), and fibrochondromatous hamartomas, a lesion unrelated to emphysema.9-13 Placental transmogrification probably results from the development of edema, fibrosis, and chronic inflammation in the residual alveolar tissues of patients with severe emphysema. Xu et al13 identified placental transmogrification changes in 6 of 38 cases of fibrochondromatous hamartomas and suggested that the villous microscopic changes may have been induced by a proliferation of the epithelial cells lining the hamartomas. The development of fatty infiltration within these lesions is even more intriguing. Hochholzer et al10 suggested that the presence of lipomatous change in patients with emphysema and placental transmogrification may be the result of metaplastic mesenchymal differentiation.

References

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13. Xu R, Murray M, Jagirdar J, Delgado Y, Melamed J. Placental transmogrification of the lung is a histologic pattern frequently associated with pulmonary fibrochondromatous hamartoma. Arch Pathol Lab Med. 2002;126:562-566.

14. Trimis G, Theodoridou M, Mostrou G, Kakavakis K. Swyer-James (MacLeod’s) syndrome following pertussis infection in an infant. Scand J Infect Dis. 2003;35:197-199.

15. Fregonese L, Girosi D, Battistini E, et al. Clinical, physiologic, and roentgenographic changes after pneumonectomy in a boy with Macleod/Swyer-james syndrome and bronchiectasis. Pediatr Pulmonol. 2002;34:412-416.

Alberto M. Marchevsky, MD; Rogelio Guintu, MD; Michael Koss, MD; Clark Fuller, MD; Ward Houck, MD; Robert J. McKenna, MD

Accepted for publication December 7, 2004.

From the Departments of Pathology and Laboratory Medicine (Drs Marchevsky and Guintu) and Thoracic Surgery (Drs Fuller, Houck, and McKenna), Cedars-Sinai Medical Center, Los Angeles, Calif; and the Department of Pathology, University of Southern California, Los Angeles (Dr Koss).

The authors have no relevant financial interest in the products or companies described in this article.

Reprints: Alberto Marchevsky, MD, Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90048 (e-mail: marchevsky@cshs.org).

Copyright College of American Pathologists May 2005