Case In Point: Polydipsia, polyuria, and pneumothorax in a young woman with diffuse cystic lung lesions

The authors describe a patient who was initially thought to have lymphangioleiomyomatosis (LAM). However, further diagnostic tests, which included lung biopsy, yielded a different diagnosis.

The case

A 23-year-old woman was referred to our interstitial lung disease (ILD) clinic with a diagnosis of LAM, a progressive cystic ILD that affects women of childbearing age. The patient had been a smoker since the age of 16, but she quit smoking about 2 months before the clinic visit, when she had a pneumothorax. At that time, she complained of sudden onset right-sided chest pain with shortness of breath for which she was admitted to her hometown hospital.

A chest tube was placed with successful drainage of the pneumothorax. A chest CT scan showed multiple lucent cystic lesions with thin walls throughout both lungs, predominantly in the upper lobes. She was discharged home after 3 days with a presumed diagnosis of LAM.

During her visit to our clinic, she complained of mild dyspnea on exertion with some discomfort at the site of chest tube insertion. She also complained of polydipsia and polyuria. She had no significant occupational history. She worked as a waitress in a steakhouse restaurant. Findings from her physical examination were unremarkable. Lungs were clear to auscultation without wheezing or crackles.

•Imaging studies: Chest radiographs showed diffuse reticular abnormalities throughout the middle and lower fields (Figure 1).High-resolution chest CT scans showed multiple irregular lucent cystic lesions with thin walls throughout both lungs, predominantly in the upper lobes; no lymphadenopathy was present (Figure 2). Findings on an abdominal CT scan were unremarkable, without evidence of renal angiomyolipomas. Because of the history of polydipsia and polyuria, she underwent head MRI; the findings were normal.

•Pulmonary function tests and laboratory studies: Pulmonary function testing showed a functional residual capacity of 3.77 L (108% of predicted value), forced expiratory volume in 1 second of 3.06 L (98% of predicted value), total lung capacity of 5.47 L (112% of predicted value), and residual volume of 1.70 L (134% of predicted value). The flow-volume loop appeared to be normal. Carbon monoxide-diffusing capacity was 14.0 (62%).

Routine laboratory work and a₁-antitrypsin levels were within normal range. Test results for antinuclear antibody, rheumatoid factor, antineutrophil cytoplasmic antibody, SCL-70 antibody, and Anti-Jo antibodies were negative.

•Differential diagnosis: Based on the clinical presentation and the CT findings, the patient was thought to have LAM. However, the polydipsia and polyuria suggested diabetes insipidus, which is seen in 15% of patients with pulmonary eosinophilic granuloma, another chronic cystic disease of the lungs seen in young patients who smoke. The nature of the cystic lesions seen on the CT scans also suggested a diagnosis of eosinophilic granuloma. Desquamative interstitial pneumonia and respiratory bronchiolitis- related ILD were also considered because they are smoking-related ILDs; however, they rarely present with cystic lung lesions and pneumothorax. To obtain a histologic diagnosis, a video-assisted thoracoscopic lung biopsy was planned.

•Lung biopsy: The specimen obtained by thoracoscopy showed a large number of intrapulmonary Langerhans cells, which were positive for cytoplasmic S-100 protein and CD1a, clustered around areas of cystic changes consistent with Langerhans cell histiocytosis. An immunostain for HMB-45 was negative, arguing against the possibility of LAM (Figure 3).

In view of these findings, the patient was given a diagnosis of pulmonary Langerhans cell histiocytosis, and she was advised to not smoke and to avoid smoky or dusty environments. This case highlights the importance of a careful history and examination, imaging studies, and tissue histology in distinguishing cystic interstitial lung disorders in young patients.

Discussion

Primary pulmonary Langerhans cell histiocytosis (also known as histiocytosis X, pulmonary Langerhans granulomatosis, or eosinophilic granuloma of the lungs) is an uncommon ILD that primarily affects young adults.¹ The true incidence and prevalence are unknown. However, the estimated annual incidence ranges from 0.5 to 5.4 cases per million persons per year.

No occupational or geographic predisposition has been reported, but nearly all affected persons have a history of current or past cigarette smoking. The pathogenesis of pulmonary Langerhans cell histiocytosis is unknown. However, cigarette smoking is considered to play an important role for the following reasons. First, tobacco increases bombesin-like peptide production. Bombesin is a neuropeptide produced by neuroendocrine cells, which are increased in the lungs of smokers.² Bombesin-like peptides are chemotactic for monocytes and are mitogenic for epithelial cells and fibroblasts, and they stimulate cytokine secretion.

Second, tobacco glycoprotein induces lymphocyte differentiation and lymphokine production and may contribute to disease pathogenesis.³ Thus, pulmonary Langerhans cell histiocytosis may represent an inflammatory reactive polyclonal proliferation of the Langerhans cells that are induced by stimulants in cigarette smoke.⁴

Adults with pulmonary Langerhans cell histiocytosis can present in a variety of ways. Approximately 20% of patients are asymptomatic at presentation. However, nonproductive cough and shortness of breath are the most common presenting complaints, and constitutional symptoms, such as weight loss, fever, night sweats, and anorexia, occur in up to a third of patients. A number of patients may present with a spontaneous pneumothorax, as seen in our patient.

The presence of ILD in a young person with a history of pneumothorax is described as a classic presentation for pulmonary Langerhans cell histiocytosis, although it occurs in a minority of patients (10% to 15%). Hemoptysis is rare. Other, less common symptoms and signs include chest pain, pain associated with bone involvement, polyuria and polydipsia related to hypothalamic involvement, rashes, adenopathy, and abdominal discomfort resulting from infiltration of the liver and spleen.^5,6

Surgical lung biopsy is considered the gold standard in the diagnosis of pulmonary Langerhans cell histiocytosis. It is possible to establish the diagnosis via bronchoscopy with transbronchoscopic lung biopsy in only 10% to 40% of cases, although this approach may still be useful in some cases by providing an alternative diagnosis, such as sarcoidosis, hypersensitivity pneumonitis, or infections.

Perhaps the most compelling reason for bronchoscopy in the workup is to perform bronchoalveolar lavage (BAL). The presence of 5% or more cells that stain with the CD1a marker (a specific marker for Langerhans type cells) makes the diagnosis of pulmonary Langerhans cell histiocytosis very likely in the appropriate clinical setting. If bronchoscopy with BAL and high-resolution CT cannot confirm the diagnosis, surgical lung biopsy may be necessary.⁷

Pulmonary Langerhans cell histiocytosis is a challenging disease to manage because of lack of well-defined prognostic indicators and limited understanding of the natural history of disease. A critical component of management is smoking cessation. Immunosuppressive therapies, such as corticosteroids and cytotoxic agents, are of limited value. Lung transplantation should be considered in patients with advanced and progressive disease unless contraindications are present.

Recurrence of the condition in the transplanted lung may occur.⁸ In one study, the median survival was 12.5 years from diagnosis. Estimated 5- and 10-year survival rates were 74% and 64%, respectively, according to the collected Mayo Clinic experience of 102 adults with pulmonary Langerhans cell histiocytosis.⁹

Pulmonary Langerhans cell histiocytosis is an uncommon ILD that primarily affects young adults. It may present with spontaneous pneumothorax or incidental findings on chest imaging. Its pathogenesis is likely related to tobacco smoke, and smoking cessation is essential in the management of this disease.

References:

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