DOI: 10.1148/rg.271065044
RadioGraphics 2007;27:265-268
© RSNA, 2007
Best Cases from the AFIP
Pulmonary Langerhans Cell Histiocytosis1
Danny L. Leatherwood, MD,
Darel E. Heitkamp, MD and
Robert E. Emerson, MD
1 From the Division of Neuroradiology, Barrow Neurological Institute, St Joseph’s Hospital and Medical Center, 350 W Thomas Rd, Phoenix, AZ 85013 (D.L.L.); the Department of Radiology, Indiana University School of Medicine, University Hospital, Indianapolis (D.E.H.); and the Department of Pathology, Indiana University School of Medicine, Wishard Memorial Hospital, Indianapolis (R.E.E.). Received March 28, 2006; revision requested May 1 and received August 28; accepted August 31. D.E.H. receives research support from Spiration, Redmond, Wash, and his department has a contract with Koninklijke Philips Electronics, Amsterdam, The Netherlands; all other authors have no financial relationships to disclose.
Address correspondence to D.L.L. (e-mail: dan.leatherwood{at}gmail.com).
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History
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A 21-year-old woman presented to the emergency department with a 1-month history of sore throat and a 9-month history of worsening nonproductive cough. She had been provisionally diagnosed with asthma 9 months earlier, but her cough had not responded to treatment with a fluticasone inhaler. She reported dyspnea only after prolonged coughing episodes. She admitted smoking one pack of cigarettes per day for the past 3 years and has three paternal uncles with 
1-antitrypsin deficiency. At admission, she appeared to be in no acute distress. Coarse breath sounds were heard throughout both lungs at physical examination, and the blood oxygen saturation measured 88% with room air. Her serum 1-antitrypsin level was normal.
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Imaging Findings
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Initial posteroanterior chest radiographs revealed diffuse cystic changes and reticular opacities throughout the lungs (Fig 1). The lung volumes were normal. High-resolution computed tomography (CT) images demonstrated widespread small, thin-walled lung cysts with resultant parenchymal destruction (Fig 2). All lobes were involved with relative sparing of the costophrenic angles (Fig 2d). Cysts in the apical segments were relatively thicker walled, measuring 2–4 mm in wall thickness (Fig 2a). No discrete lung nodules were present. There was no pneumothorax, pleural effusion, or thoracic lymphadenopathy.
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Figure 1a. (a) Posteroanterior radiograph of the chest shows widespread cystic changes in the lungs and subsequent diffuse reticular opacities produced by the overlapping cysts. (b) Magnified view of the right upper lung shows the confluent superimposed lung cysts in detail.
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Figure 1b. (a) Posteroanterior radiograph of the chest shows widespread cystic changes in the lungs and subsequent diffuse reticular opacities produced by the overlapping cysts. (b) Magnified view of the right upper lung shows the confluent superimposed lung cysts in detail.
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Figure 2a. High-resolution CT images (lung windows) show diffuse lung cysts with associated parenchymal destruction. (a) The apical cysts have thicker walls. (b) Predominantly thin-walled cysts of various shapes and sizes are packed throughout the middle and upper lungs. (c, d) There is relative sparing of the lung bases (c) and costophrenic angles (d).
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Figure 2b. High-resolution CT images (lung windows) show diffuse lung cysts with associated parenchymal destruction. (a) The apical cysts have thicker walls. (b) Predominantly thin-walled cysts of various shapes and sizes are packed throughout the middle and upper lungs. (c, d) There is relative sparing of the lung bases (c) and costophrenic angles (d).
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Figure 2c. High-resolution CT images (lung windows) show diffuse lung cysts with associated parenchymal destruction. (a) The apical cysts have thicker walls. (b) Predominantly thin-walled cysts of various shapes and sizes are packed throughout the middle and upper lungs. (c, d) There is relative sparing of the lung bases (c) and costophrenic angles (d).
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Figure 2d. High-resolution CT images (lung windows) show diffuse lung cysts with associated parenchymal destruction. (a) The apical cysts have thicker walls. (b) Predominantly thin-walled cysts of various shapes and sizes are packed throughout the middle and upper lungs. (c, d) There is relative sparing of the lung bases (c) and costophrenic angles (d).
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Pathologic Evaluation
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Video-assisted thoracoscopic surgery was performed to obtain diagnostic wedge biopsy specimens of the right upper and right lower lobes. At low power (x 100), the tissue was composed of a densely cellular infiltrate of histiocytes and other inflammatory cells within the interstitium and the airspaces (Fig 3). Normal lung tissue was present in the upper right corner of the field. At higher magnification (x 600), sheets of histiocytes with abundant pale, eosinophilic cytoplasm were apparent (Fig 4). Some histiocytes had large and irregular nuclei and longitudinal nuclear grooves. Numerous eosinophils were seen throughout the field. Pathologic findings were consistent with pulmonary Langerhans cell histiocytosis (LCH).
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Figure 3. Low-power photomicrograph (original magnification, x100; hematoxylineosin stain) of the sampled lung tissue shows a densely cellular infiltrate of histiocytes and other inflammatory cells within the interstitium and airspaces (lower left). Normal lung tissue is present at the upper right.
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Figure 4. High-power photomicrograph (original magnification, x600; hematoxylineosin stain) shows sheets of histiocytes with abundant pale, eosinophilic cytoplasm (arrows). Numerous eosinophils are also seen throughout the field (arrowheads).
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Discussion
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Dendritic cells are components of the mammalian immune system that are chiefly located in tissues that contact the external environment, such as the skin, lungs, and gastrointestinal tract. These cells detect and phagocytize pathogenic organisms and then present protein fragments of these pathogens on their cell surfaces as antigens, able to stimulate both T- and B-cell immune responses. Langerhans cells are a subset of dendritic cells located in the epidermal layer of the skin that were described by Paul Langerhans in the late 1860s. These cells are unique among dendritic cells as they contain Birbeck granules, distinctive "tennis racket"–shaped granules described by Michael Birbeck in 1961 (1). Once phagocytosis and antigen processing have begun, all dendritic cells, including Langerhans cells, function by maturing and traveling to local draining lymph nodes for presentation of the surface antigens to T and B lymphocytes.
LCH was formerly known by various names such as histiocytosis X, eosinophilic granuloma, Letterer-Siwe disease, and Hand-Schüller-Christian syndrome (2). LCH is an abnormal nonmalignant proliferation of monoclonal Langerhans cells within one or multiple organ systems (3). Although the etiology of LCH is unknown, theories include viral infection, antigen exposure, and somatic mutation (1).
Pulmonary LCH refers to LCH isolated to the respiratory system, notably the lungs. This rare disease is found almost exclusively in cigarette smokers, which supports the theory of antigen exposure, since cigarette smoke contains thousands of known antigens (4). Pulmonary LCH appears to begin in the third to fourth decade of life, but a patient with mild to moderate disease may not receive a diagnosis until later (5). Gender predominance has been debated in past articles. In a study by Vassallo et al (6), 102 patients with pulmonary LCH showed a female predominance of 61%. The most common clinical symptoms include dyspnea, cough, and fatigue (6), although patients may present with chest pain caused by a pneumothorax. Results of a respiratory examination are usually normal or nonspecific. Rales, wheezing, or decreased breath sounds can be auscultated (1). Pulmonary function tests may reveal an obstructive, restrictive, or mixed pattern. A decrease in carbon monoxide diffusing capacity is present in up to 90% of patients (1,4).
The radiologic findings of pulmonary LCH vary depending on the stage of the disease at diagnosis. Diffuse bilateral ill-defined nodules will be seen in early stages. Because the disease has an inhalational component, the middle and upper lung zones are involved to a greater extent than the lung bases. It is thought that these nodules undergo cystic degeneration as the disease progresses, and so a reticular pattern begins to predominate on chest radiographs as the numerous cystic walls are superimposed on one another (5). The cysts and residual parenchyma can undergo fibrosis over time and eventually lead to changes of honeycombing (1). High-resolution CT plays an important role in the evaluation of pulmonary LCH. The diagnosis can be easily made with high-resolution CT by showing both ill-defined nodules and cysts in a heavy smoker. However, the diagnostic accuracy of high-resolution CT falls short when only nodules or cysts alone are present. Most of these cases are confirmed with lung biopsy (5). In a study of 92 patients with chronic cystic lung disease, Koyama et al (7) achieved a diagnostic accuracy of 72% for diagnosis of pulmonary LCH with high-resolution CT alone.
The differential diagnosis of primarily cystic lung disease includes predominantly cystic pulmonary LCH, lymphangiomyomatosis, emphysema, and bronchiectasis. The cysts in LCH are often variable in size and wall thickness. Some authors have postulated that the natural history of pulmonary LCH is a progression from early-stage nodules to cavitary nodules, to thick-walled cysts, and finally to thin-walled cysts. Like the nodules that precede them, the cysts tend to be most numerous in the upper and middle lung zones and spare the lung bases. The early involvement of distal bronchioles often leads to an obstructive pattern of lung disease on chest radiographs, a finding that translates into normal or increased lung volumes despite the fibrosing nature of the disease. The cysts of lymphangiomyomatosis can resemble those of pulmonary LCH, but they occur diffusely throughout the lungs and affect women almost exclusively. The cystic cavities of emphysema represent foci of destroyed parenchyma and lack definable walls. The cystlike bronchial dilatation seen in bronchiectasis can be distinguished by the communicating branching pattern seen on contiguous CT images (1).
For most patients, symptom stabilization occurs with smoking cessation alone. Corticosteroid therapy has also led to disease stabilization in some studies, although this approach has not been compared with the efficacy of smoking cessation alone. In patients with rapid deterioration of pulmonary function, lung transplantation is an option, although smoking cessation needs to be demonstrated for consideration, as pulmonary LCH can recur if the patient continues to smoke (1). The patient presented in this case report failed to keep scheduled pulmonology appointments following her biopsy and presently continues to show up intermittently at the emergency department complaining of shortness of breath. She continues to smoke and has completed only short trials of oral steroids after being discharged from the emergency department.
Patients with pulmonary LCH have variable and uncertain clinical courses. Up to one-half will show clinical and radiographic stability, while up to 25% will demonstrate spontaneous regression. The remaining 25% can have continued cystic replacement of parenchyma that may progress to end-stage lung disease. Adults with the disease have decreased overall long-term survival compared to those without the disease (6). Mortality from pulmonary LCH can occur due to pulmonary hypertension or respiratory failure. Although there is a strong association with cigarette smoking, there is no known link between relapse of disease and continuation of smoking or between regression of disease and cessation of smoking (1).
The Histiocyte Society maintains an international registry of patients with LCH at http://histio.org/society. At this Web site, patients can be added to the registry and information can be obtained about current experimental protocols available for patients with different forms of LCH, including those with primary lung involvement.
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Footnotes
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Abbreviations: LCH = Langerhans cell histiocytosis
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References
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- Abbott GF, Rosado-de-Christenson ML, Franks TJ, Frazier AA, Galvin JR. Pulmonary Langerhans cell histiocytosis. RadioGraphics 2004;24:821–841.[Abstract/Free Full Text]
- Favara BE, Feller AC, Pauli M, et al. Contemporary classification of histiocytic disorders. Med Pediatr Oncol 1997;29:157–166.[CrossRef][Medline]
- Willman CL, Busque L, Griffith BB, et al. Langerhans’-cell histiocytosis (histiocytosis X): a clonal proliferative disease. N Engl J Med 1994;331:154–160.[Abstract/Free Full Text]
- Vassallo R, Ryu JH, Colby TV, Hartman T, Limper AH. Pulmonary Langerhans’-cell histiocytosis. N Engl J Med 2000;342:1969–1978.[Free Full Text]
- Sundar KM, Gosselin MV, Chung HL, Cahill BC. Pulmonary Langerhans cell histiocytosis: emerging concepts in pathobiology, radiology, and clinical evolution of disease. Chest 2003;123:1673–1683.
- Vassallo R, Ryu JH, Schroeder DR, Decker PA, Limper AH. Clinical outcomes of pulmonary Langerhans’-cell histiocytosis in adults. N Engl J Med 2002;346:484–490.[Abstract/Free Full Text]
- Koyama M, Johkoh T, Honda O. Chronic cystic lung disease: diagnostic accuracy of high-resolution CT in 92 patients. AJR Am J Roentgenol 2003;180: 827–835.[Abstract/Free Full Text]
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History
Imaging Findings
