Pulmonary Langerhans' cell histiocytosis

Pulmonary Langerhans' cell histiocytosis (PLCH) remains an important diagnostic consideration in the differential diagnosis of diffuse infiltrative lung disease, particular among smokers. This review highlights recent progress in our understanding of the etiology, clinical presentation, and diagnostic and therapeutic approaches to this unusual lung disorder. Evolving studies strongly link the basic pathogenesis of PLCH as an uncommon reaction to tobacco smoke. Recent progress in the clinical approach to these patients has emphasized important roles for high-resolution computed tomographic (CT) scanning and immune reactive tissue markers including cluster differentiation (CD) 1a antigen in the diagnosis of this disorder. A rationale diagnostic algorithm and current management strategies are summarized.     

Pulmonary Langerhans' cell histiocytosis (histiocytosis X) following metastasizing malignant melanoma

BACKGROUND: Pulmonary Langerhans' cell histiocytosis (histiocytosis X) is an uncommon, diffuse interstitial lung disease of unknown cause, mostly presenting in young smokers. Association of pulmonary Langerhans' cell histiocytosis with a malignant neoplasm is rare. CASE DESCRIPTION AND RESULTS: We present and discuss the case of a 48-year-old man (ex-smoker) with metastasising malignant melanoma. A few months after chemotherapy and a modified Whipple procedure for retroduodenal metastasis of a malignant melanoma, computer tomographic scans revealed intrapulmonary "ring-shaped structures". Endobronchial biopsies and bronchioalveolar lavage showed no evidence of neoplasm or inflammation. Open-lung biopsy was performed and revealed pulmonary Langerhans' cell histiocytosis. CONCLUSION: To our knowledge this is the first reported case of pulmonary Langerhans' cell histiocytosis in association with malignant melanoma. Chemotherapy for malignant melanoma may be related to the development of pulmonary Langerhans' cell histiocytosis.     

Pulmonary Langerhans' cell histiocytosis presenting with an endobronchial lesion

A 19-year-old man visited our hospital complaining of cough, sputum and low-grade fever. Chest radiograph and computed tomography findings suggested that he was suffering from pulmonary Langerhans' cell histiocytosis (PLCH). Bronchoscopy revealed a whitish elevated lesion at the bifurcation of the right upper lobe bronchus, and a specimen of this lesion showed the same pathological findings as pulmonary parenchymal lesions. Although there have been only a few reports of endobronchial LCH without pulmonary parenchymal lesions, this is, to our knowledge, the first case of PLCH with an endobronchial lesion, which was confirmed by bronchoscopy, and disappeared several months later.     

Pulmonary Langerhans' cell histiocytosis: radiologic resolution following smoking cessation.

We describe two patients with histologically proven pulmonary Langerhans' cell histiocytosis in whom radiologic improvement occurred following smoking cessation. The patients had 23- and 25-pack-year smoking histories, respectively. High-resolution CT revealed multiple small nodules, located predominantly in the upper and middle lung fields. There was a close temporal relationship between smoking cessation and radiologic improvement.     

Adult pulmonary Langerhans' cell histiocytosis

INTRODUCTION: Adult pulmonary Langerhans'cell histiocytosis, also referred to as histiocytosis X, is a disorder of unknown etiology which affects preferentially young smokers. The disease is characterized by granulomatous lesions which progressively invade and destroy distal airways, leading to the formation of characteristic cicatricial kystic lesions. Florid granulomas contain numerous Langerhans'cells, antigen-presenting cells of the dendritic cell lineage, associated with T lymphocytes and eosinophils. The diagnosis rests on the combination of clinical and radiologic data, and particularly on high-resolution CT scan findings showing a typical association of nodular and cystic changes, predominantly in the upper and middle lobes. Further evaluation with surgical lung biopsy is indicated in less typical situations. CURRENT KNOWLEDGE AND KEY POINTS: The pathogenesis of Langerhans'cell histiocytosis is not fully understood, but several arguments suggest that the disease results from an abnormal immune reaction initiated by Langerhans'cells and directed against the bronchial epithelium. Other arguments suggest the presence of genetic abnormalities susceptible, for example, to increase the sensitivity of these cells to cytokines (GM-CSF, or others) known to influence their survival and maturation. FUTURE PROSPECTS AND PROJECTS: These recent advances in the pathogenesis of Langerhans'cell histiocytosis could promote the development of new therapeutic strategies designed to regulate the number and activated state of Langerhans'cells in specific lesions.     

Adult pulmonary Langerhans' cell histiocytosis.

Adult pulmonary Langerhans' cell histiocytosis is a rare disorder of unknown aetiology that occurs predominantly in young smokers, with an incidence peak at 20-40 yrs of age. In adults, pulmonary involvement with Langerhans' cell histiocytosis usually occurs as a single-system disease and is characterised by focal Langerhans' cell granulomas infiltrating and destroying distal bronchioles. High-resolution computed tomography (HRCT) of the chest is essential to the diagnosis, typically showing a combination of nodules, cavitated nodules, and thick- and thin-walled cysts. A high macrophage count in bronchoalveolar lavage (BAL) fluid is a common but nonspecific finding that merely reflects exposure to tobacco smoke. BAL is useful for eliminating infections and the other infiltrating lung disorders that can be seen in young adults. Langerhans' cells can be identified in BAL fluid, but, in contrast to what was initially hoped, this test shows a very low sensitivity and is rarely useful in the diagnosis of the disease. The definite diagnosis of pulmonary Langerhans' cell histiocytosis requires identification of Langerhans' cell granulomas, which is usually achieved by surgical lung biopsy at a site selected by chest HRCT. In practice, however, lung biopsy is performed on a case-by-case basis. No effective treatment is available to date, and improved understanding of the mechanisms involved in the pathogenesis of pulmonary Langerhans' cell histiocytosis is urgently needed, and should help in the development of specific therapeutic strategies for patients with this orphan disease.     

Langerhans' cell histiocytosis of the liver in adults

Among adults, liver involvement is relatively frequent in Langerhans' cell histiocytosis (LCH), even though it is often overlooked. In fact, the liver involvement may be missed in apparently localized LCH or when it is the sole site of involvement. We present 23 cases of liver involvement in LCH out of a cohort study of 85 adult patients included in the French Histiocytosis Study Group Registry. The most frequent clinical setting was multiorgan involvement (87% of our cases). The main histological pattern in liver LCH was sclerosing cholangitis (56% of the cases). The symptoms included hepatomegaly (48%) and/or liver biochemistry abnormalities (61%, including cholestasis associated with increased transaminases levels in 35% of cases, cholestasis only in 22% and increased transaminases levels only in 4% of the cases). Particularly suggestive of the diagnosis was the observation of biliary tree abnormalities through magnetic resonance imaging (MRI). The natural history of liver LCH fits into two stages: early infiltration by histiocytes and late sclerosis of the biliary tree. We found that liver involvement had a significant impact on survival. Thus we suggest that clinical and biological liver evaluation must be performed regularly onwards to screen every LCH adult patient from the time of the initial diagnosis. MRI and liver biopsy should be considered as soon as the data point to a possible liver localization. If this diagnosis is confirmed, we suggest a treatment with ursodesoxycholic acid, as in other cholestatic diseases, together with treatments specifically directed towards LCH. However, the ideal treatment of liver LCH remains to be found, and in advanced cases transplantation is the sole option.     

Multisystem Langerhans' cell histiocytosis with pancreatic involvement.

Langerhans' cell histiocytosis, a rare disorder of unknown cause affecting both children and adults, can affect many different organs and present to a wide range of medical specialties. An infant with fatal multisystem Langerhans' cell histiocytosis in whom the pancreas and the intestine were extensively affected is reported. The direct pancreatic involvement by this disease has not previously been described.     

A case of pulmonary Langerhans' cell histiocytosis]

A 42-yr-old woman was referred to our hospital because of multiple small nodules in a chest radiograph. She had no symptoms such as dyspnea, cough or sputum. A chest CT revealed many centrilobular small nodules and thin-walled cysts with predominance in the peripheral area of the lungs. The specimens obtained by thoracoscopic surgery showed granulomas with scattered eosinophils and numerous Langerhans' cells. The Langerhans' cells were positive for both S-100 protein and CD1a. These findings are compatible with pulmonary Langerhans' cell histiocytosis (LCH). Since the granulomas showed no fibrotic changes, the LCH may have been in its early stages. However, there were clusters of lymphocytes and macrophages around the terminal and respiratory bronchioles, and cystic lesions without cellular infiltrates, in the specimens. The former histologic findings suggested respiratory bronchiolitis causing interstitial lung disease and the latter are indistinguishable from centrilobular emphysema. Therefore, these smoking-related diseases may have been superimposed on the LCH in this patient.     

Thyroid involvement by malignant histiocytosis of Langerhans' cell type

Involvement of the thyroid gland by Langerhans' cell histiocytosis is quite rare. We describe the case of a 58-year-old man referred for treatment of a progressively enlarging goitre. The trachea was severely stenotic and adjacent structures such as the left carotid vein and the thyroid cartilage were also involved. Central diabetes insipidus and severe combined immunodeficiency were associated. Although fine needle aspiration biopsy of the thyroid was initially interpreted as papillary carcinoma, anaplastic thyroid cancer was suspected. Treatment with prednisolone, doxorubicin and irradiation controlled the tracheal compression. A diagnosis of thyroid Langerhans' cell histiocytosis was finally made on the basis of the presence of Birbeck granules and CD1a and CD4 antigen in the thyroid tumour cells. Furthermore, positive staining for CD68 and lysozyme suggested that the tumour cells may have had the character of phagocytic cells in addition to their dendritic cell nature. This is the first case of thyroid involvement by malignant histicytosis of Langerhans' cell type with unusual phagocytic markers.     

Growth and endocrine disorders in multisystem Langerhans' cell histiocytosis

INTRODUCTION: Langerhans' cell histiocytosis is a rare disorder, with diabetes insipidus occurring in up to half of patients. Causes of growth failure include the illness itself, treatments used and growth hormone insufficiency. PATIENTS AND METHODS: We identified all patients with an endocrinopathy secondary to Langerhans' cell histiocytosis (LCH). Growth data were analysed from all patients with multisystem involvement. RESULTS: Of 144 patients with multisystem LCH, 50 had an endocrinopathy, 49 of whom had diabetes insipidus. Growth hormone insufficiency (GHI) was present in 21 patients, seven of whom had other anterior pituitary deficiencies as well (gonadotrophin deficiency + GHI n = 2, gonadotrophin deficiency + TSH deficiency + GHI n = 2, panhypopituitarism n = 3). GH insufficiency, the development of which appeared to be independent of pituitary radiation, occurred at a median age of 8.3 years (4.7-18 years) and at a median interval of 3.5 years (0-11.8 years) after diagnosis of LCH. The median height SDS at diagnosis of growth hormone insufficiency was -2.9. Thirteen of the patients with growth hormone insufficiency attained final height with a median height SDS of -1.2. The final height SDS of 15 patients without GH insufficiency was closer to target height SDS, but not statistically different from that of the GH insufficient group. CONCLUSIONS: GH therapy significantly improves growth in GH insufficient patients with Langerhans' cell histiocytosis. Early institution of GH therapy may further improve height outcome. However, most children with Langerhans' cell histiocytosis regardless of endocrine function, failed to reach target height.     

Langerhans' cell histiocytosis mimicking metastatic carcinoma of the lung

Langerhans' cell histiocytosis (LCH), previously known as Histiocytosis X, is characterized by abnormal accumulations of large mononuclear cells forming granulomas in various organs, mainly bone, skin and lung. This case report describes a 50-year-old man with a history of left pneumonectomy due to squamous cell carcinoma (SCC). During routine follow up, a CXR showed new parenchymal nodules in the right lung 57 months post treatment. Chest CT scan confirmed the presence of multiple parenchymal nodules. Open lung biopsy from the right upper lobe was performed and LCH was diagnosed. Re-analysis of the initial pneumonectomy specimen revealed no evidence of LCH in the surrounding lung tissue. On diagnosis, the patient stopped smoking and was treated with vinblastine and prednisolone for LCH. The nodules disappeared and have not returned in a further 18 months of follow up. In this patient LCH was diagnosed after SCC, which highlights that smoking-related diseases can be seen concomitantly or sequentially in the same patient.     

A case of multiorgan Langerhans' cell histiocytosis presented with pneumothorax

Pulmonary Langerhans' cell histiocytosis (LCH) represents an uncommon clinical disorder with unpredictable clinical presentation and outcome. Lung involvement may occur either in isolation or as part of a multiorgan disease. A 43-year-old woman was admitted to our hospital with acute left chest pain and shortness of breath. Spontaneous left pneumothorax was detected. All laboratory tests, including pulmonary function studies, were normal. Radiological findings posed high suspicion for LCH and lung biopsy confirmed this diagnosis. Further studies identified small cystic lesions in the scalp and liver. The diagnosis of multiple organ LCH involvement was made. Spontaneous pneumothorax might be the presenting clinical symptom of LCH. The present case emphasizes the capricious nature of LCH and the importance of an individualized therapeutic approach.     

A case of disseminated Langerhans' cell histiocytosis treated with thalidomide

Tumor necrosis factor alpha (TNF-alpha) seems to play a key role in the pathogenesis of Langerhans' cell histiocytosis (LCH). Thalidomide is an immunomodulator agent of inflammatory cytokines including TNF-alpha. To our knowledge this is the first case of disseminated LCH successfully treated with thalidomide.