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Pulmonary Langerhans Cell Histiocytosis Presenting as a Solitary Nodule

2001; Elsevier BV; Volume: 76; Issue: 2 Linguagem: Inglês

10.4065/76.2.209

1942-5546

András Khoór, Jeffrey L. Myers, Henry D. Tazelaar, Stephen J. Swensen,

Viral-associated cancers and disorders

Solitary pulmonary nodules are an uncommon manifestation of pulmonary Langerhans cell histiocytosis (PLCH). We describe a 45-year-old male cigarette smoker who presented with an asymptomatic solitary pulmonary nodule that showed histologic and immunophenotypic characteristics of PLCH. Twenty-one years after excision of the nodule, at the age of 66 years, he is asymptomatic with a new contralateral lung nodule but no evidence of interstitial disease. The new nodule has remained unchanged after 36 months of observation. This case affirms that PLCH can occasionally cause solitary lesions, which should not be interpreted as a harbinger of interstitial lung disease. Isolated PLCH should be included in the differential diagnosis of unusual solitary pulmonary nodules. Solitary pulmonary nodules are an uncommon manifestation of pulmonary Langerhans cell histiocytosis (PLCH). We describe a 45-year-old male cigarette smoker who presented with an asymptomatic solitary pulmonary nodule that showed histologic and immunophenotypic characteristics of PLCH. Twenty-one years after excision of the nodule, at the age of 66 years, he is asymptomatic with a new contralateral lung nodule but no evidence of interstitial disease. The new nodule has remained unchanged after 36 months of observation. This case affirms that PLCH can occasionally cause solitary lesions, which should not be interpreted as a harbinger of interstitial lung disease. Isolated PLCH should be included in the differential diagnosis of unusual solitary pulmonary nodules. Pulmonary eosinophilic granuloma, also known as Langerhans cell granulomatosis, Langerhans cell histiocytosis, and histiocytosis X, is an interstitial lung disease characterized by an abnormal proliferation of Langerhans cells.1Myers JL Colby TV Yousem SA Common pathways and patterns of injury.in: Dail DH Hammar SP Pulmonary Pathology. 2nd ed. Springer-Verlag, New York, NY1994: 57-77Crossref Google Scholar Most patients are cigarette smokers in their third and fourth decades of life. Men are more commonly affected than women, by a ratio of 1.5:1. Characteristically, patients present with nonspecific respiratory complaints and bilateral reticulonodular infiltrates. Presentation as a solitary pulmonary nodule is rare.2Fichtenbaum CJ Kleinman GM Haddad RG Eosinophilic granuloma of the lung presenting as a solitary pulmonary nodule.Thorax. 1990; 45: 905-906Crossref PubMed Scopus (19) Google Scholar, 3Hammar SP Pulmonary histiocytosis X (pulmonary Langerhans' cell granulomatosis).in: Dail DH Hammar SP Pulmonary Pathology. 2nd ed. Springer-Verlag, New York, NY1994: 567-596Crossref Google Scholar, 4ten Velde GPM Thunnissen FBJM Van Engelshoven JMA Wouters EFM A solitary pulmonary nodule due to eosinophilic granuloma.Eur Respir J. 1994; 7: 1539-1540Crossref PubMed Scopus (14) Google Scholar We describe a patient who underwent excisional biopsy of a solitary nodule of pulmonary Langerhans cell histiocytosis (PLCH) 24 years previously. A 45-year-old male cigarette smoker presented with an asymptomatic solitary pulmonary nodule in the left upper lobe. He underwent thoracotomy and wedge excision of the lesion. After the operation, he continued to smoke. Twenty-one years later, at the age of 66 years, he presented with a new asymptomatic solitary nodule in the right upper lobe. Computed tomography showed only a single pulmonary nodule with no evidence of interstitial lung disease. Since the second lesion was benign by radiographic criteria, no biopsy was performed. His diffusing capacity for carbon monoxide was normal (84% of predicted) 21 years after his initial surgery. Pulmonary function tests 23 years after his initial surgery showed mild obstruction with a reduced forced expiratory volume in 1 second (2.49 L/s, 60% of predicted) and a forced expiratory volume in 1 second-forced vital capacity ratio (66.7) at the lower limits of normal (>65.9). Total lung capacity was not measured. The patient's condition improved after use of inhaled bronchodilators. For 36 months, periodic radiographs showed no change in the second nodule, confirming the nodule as benign by the stability criterion (a nodule that is stable in size radiographically for at least 2 years is highly likely to be benign).5Good CA The solitary pulmonary nodule: a problem of management.Radiol Clin North Am. 1963; 1: 429-438Google Scholar, 6Good CA Wilson TW The solitary circumscribed pulmonary nodule: study of seven hundred five cases encountered roentgenologically in a period of three and one-half years.JAMA. 1958; 166: 210-215Crossref PubMed Scopus (114) Google Scholar Twenty-four years after his lung biopsy, the patient is asymptomatic with no clinical evidence or symptoms of interstitial lung disease, but he continues to smoke 1 1/2 packs of cigarettes per day. The excised nodule was well circumscribed and was 0.8 cm in greatest dimension. At low magnification, sections showed a centrally scarred, poorly circumscribed mass characterized by an irregular interface with adjacent lung tissue (Figure 1, top). The nodule comprised a combination of collagen fibrosis (as is typical for PLCH) and a variably dense inflammatory infiltrate. The most cellular zones contained a combination of eosinophils, lymphocytes, plasma cells, alveolar macrophages, and Langerhans cells (Figure 1, bottom). In many areas the eosinophils predominated and included eosinophilic microabscesses. Langerhans cells were distributed in loosely cohesive clusters and had convoluted nuclei, inconspicuous nucleoli, and abundant pale-staining eosinophilic cytoplasm with indistinct cytoplasmic borders. Lymphoid aggregates were present at the periphery of the lesion. At the interface with uninvolved lung tissue, the inflammatory infiltrate trickled into contiguous alveolar septa, imparting a scalloped appearance to the margin of the nodule. The surrounding alveoli contained pigmented (smoker's) macrophages. Paraffin-section immunostains with use of a standard peroxidase-antiperoxidase method showed strong nuclear and cytoplasmic positivity for S-100 protein (Dako, Carpenteria, Calif; dilution 1:800) and CD1a (Immunotech, Inc, West-brook, Me; 1:5 dilution) Langerhans cells. In our patient, PLCH presented as an asymptomatic solitary pulmonary nodule, a rare manifestation of this disease. To our knowledge, only 3 similar patients have been described,2Fichtenbaum CJ Kleinman GM Haddad RG Eosinophilic granuloma of the lung presenting as a solitary pulmonary nodule.Thorax. 1990; 45: 905-906Crossref PubMed Scopus (19) Google Scholar, 3Hammar SP Pulmonary histiocytosis X (pulmonary Langerhans' cell granulomatosis).in: Dail DH Hammar SP Pulmonary Pathology. 2nd ed. Springer-Verlag, New York, NY1994: 567-596Crossref Google Scholar, 4ten Velde GPM Thunnissen FBJM Van Engelshoven JMA Wouters EFM A solitary pulmonary nodule due to eosinophilic granuloma.Eur Respir J. 1994; 7: 1539-1540Crossref PubMed Scopus (14) Google Scholar only 2 in the peer-reviewed literature.2Fichtenbaum CJ Kleinman GM Haddad RG Eosinophilic granuloma of the lung presenting as a solitary pulmonary nodule.Thorax. 1990; 45: 905-906Crossref PubMed Scopus (19) Google Scholar, 4ten Velde GPM Thunnissen FBJM Van Engelshoven JMA Wouters EFM A solitary pulmonary nodule due to eosinophilic granuloma.Eur Respir J. 1994; 7: 1539-1540Crossref PubMed Scopus (14) Google Scholar Fichtenbaum et al2Fichtenbaum CJ Kleinman GM Haddad RG Eosinophilic granuloma of the lung presenting as a solitary pulmonary nodule.Thorax. 1990; 45: 905-906Crossref PubMed Scopus (19) Google Scholar described a 58-year-old man with a 42-pack-year history of cigarette smoking in whom a nodule (1.0 cm in greatest dimension) was detected in the right middle lobe on a preoperative chest radiograph. He was asymptomatic with no radiographic abnormalities 2 years later. ten Velde et al4ten Velde GPM Thunnissen FBJM Van Engelshoven JMA Wouters EFM A solitary pulmonary nodule due to eosinophilic granuloma.Eur Respir J. 1994; 7: 1539-1540Crossref PubMed Scopus (14) Google Scholar described a 42-year-old man with a 40-pack-year history of smoking and an asymptomatic solitary pulmonary nodule. At wedge resection, the nodule proved to be PLCH. No other lesions developed during a 3-year follow-up. In his textbook, Hammar3Hammar SP Pulmonary histiocytosis X (pulmonary Langerhans' cell granulomatosis).in: Dail DH Hammar SP Pulmonary Pathology. 2nd ed. Springer-Verlag, New York, NY1994: 567-596Crossref Google Scholar includes a chest radiograph of a 65-year-old man who had an isolated nodule of PLCH in the left upper lobe but provides no other information about the patient. Schönfeld et al7Schönfeld N Frank W Wenig S et al.Clinical and radiologic features, lung function and therapeutic results in pulmonary histiocytosis X.Respiration. 1993; 60: 38-44Crossref PubMed Scopus (139) Google Scholar mention 1 patient who was excluded from their review of 42 patients with PLCH. Typically, PLCH presents as bilateral reticulonodular infiltrates with or without cysts.8Lacronique J Roth C Battesti JP Basset F Chretien J Chest radiological features of pulmonary histiocytosis X: a report based on 50 adult cases.Thorax. 1982; 37: 104-109Crossref PubMed Scopus (120) Google Scholar The lesions predominate in the middle and upper lung fields, usually sparing the costophrenic angles. Although PLCH is a common cause of spontaneous pneumothorax, this probably occurs in less than 25% of patients. Unusual manifestations include intratracheal,9Pomeranz SJ Proto AV Histiocytosis X: unusual-confusing features of eosinophilic granuloma.Chest. 1986; 89: 88-92Crossref PubMed Scopus (24) Google Scholar endobronchial,10O'Donnell AE Tsou E Awh C Fallat ME Patterson K Endobronchial eosinophilic granuloma: a rare cause of total lung atelectasis.Am Rev Respir Dis. 1987; 136: 1478-1480Crossref PubMed Scopus (18) Google Scholar and mediastinal lymph node involvement.11Brambilla E Fontaine E Pison CM Coulomb M Paramelle B Brambilla C Pulmonary histiocytosis X with mediastinal lymph node involvement.Am Rev Respir Dis. 1990; 142: 1216-1218Crossref PubMed Scopus (22) Google Scholar The diagnostic feature of PLCH is proliferation of Langerhans cells. These modified macrophages are immunoreactive for S-100 protein and CD1a and contain Birbeck granules at an ultrastructural level. Immunohistochemical and electron microscopic studies of various pulmonary specimens have revealed that the presence of Langerhans cells is not limited to PLCH. Langerhans cells can reside in adenocarcinomas, squamous cell carcinomas, normal lung and various inflammatory and fibrosing conditions, eg, idiopathic pulmonary fibrosis, and hypersensitivity pneumonia. In these conditions the role of Langerhans cells is unknown, but they may have an immunologic function, such as antigen processing, and presentation to T lymphocytes. Classic lesions of PLCH may be confused histologically with usual interstitial pneumonia, desquamative interstitial pneumonia, chronic eosinophilic pneumonia, or reactive eosinophilic pleuritis,1Myers JL Colby TV Yousem SA Common pathways and patterns of injury.in: Dail DH Hammar SP Pulmonary Pathology. 2nd ed. Springer-Verlag, New York, NY1994: 57-77Crossref Google Scholar none of which were present in the current case. Rather, in the current case the differential diagnosis included forms of nonneoplastic and low-grade inflammatory masses, the main one being inflammatory pseudotumor. The term inflammatory pseudotumor (ie, also termed plasma cell granuloma or inflammatory myofibroblastic tumor) has been applied to a histologically heterogeneous group of lung lesions characterized by various combinations of mononuclear inflammatory cells and macrophages set in a fibrous stroma. In the current case, the loosely cohesive clusters of characteristic S-100 protein and CD1a-positive macrophages associated with eosinophils in a cigarette smoker helped to establish the diagnosis of PLCH. Central fibrotic scarring (as seen in this case) is characteristic of the lesions of PLCH as they age. The etiology and pathogenesis of Langerhans cell histiocytosis are poorly understood. However, a strong association exists between PLCH and cigarette smoking. Furthermore, cigarette smoking is associated with a significant increase in the number of Langerhans cells present in the pulmonary parenchyma.3Hammar SP Pulmonary histiocytosis X (pulmonary Langerhans' cell granulomatosis).in: Dail DH Hammar SP Pulmonary Pathology. 2nd ed. Springer-Verlag, New York, NY1994: 567-596Crossref Google Scholar Granulocyte-macrophage colony-stimulating factor may be partially responsible for the focal accumulation of Langerhans cells in early lesions of PLCH.12Tazi A Bonay M Bergeron A Grandsaigne M Hance AJ Soler P Role of granulocyte-macrophage colony stimulating factor (GMCSF) in the pathogenesis of adult pulmonary histiocytosis X.Thorax. 1996; 51: 611-614Crossref PubMed Scopus (59) Google Scholar Although Langerhans cell histiocytosis in non-pulmonary sites has been characterized as having features suggestive of a neoplastic process,13Willman CL Busque L Griffith BB et al.Langerhans'-cell histiocytosis (histiocytosis X)—a clonal proliferative disease.N Engl J Med. 1994; 331: 154-160Crossref PubMed Scopus (865) Google Scholar data for pulmonary PLCH are lacking. The prognosis of patients with pulmonary PLCH is generally good. A minority of patients develop progressive pulmonary disease that is ultimately fatal.3Hammar SP Pulmonary histiocytosis X (pulmonary Langerhans' cell granulomatosis).in: Dail DH Hammar SP Pulmonary Pathology. 2nd ed. Springer-Verlag, New York, NY1994: 567-596Crossref Google Scholar Factors associated with a poor prognosis include older age at diagnosis and severe airflow obstruction with air trapping. Our patient had a uniquely long clinical follow-up and was asymptomatic 24 years after surgery. Although he developed a contralateral radiographically benign solitary nodule, he had no associated interstitial disease as documented by symptoms, pulmonary function tests, or chest radiographs.