Nanette Grana1. 1. All Children's Hospital, St Petersburg, FL 33701, USA. ngrana1@jhmi.org.
Abstract
BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare histiocytic disorder of unknown etiopathogenesis. Its clinical presentation is variable and ranges from isolated skin or bone disease to a life-threatening multisystem condition. LCH can occur at any age but is more frequent in the pediatric population. A neoplastic origin of this disease has been suggested due to the discovery of the mutually exclusive activating somatic BRAF V600E and MAP2K1 gene mutations that occur in about 75% of patients. METHODS: A survey of recent literature focused on the diagnosis, management, and prognosis of Langerhans cell histiocytosis. Data were collected, analyzed, and discussed with an emphasis on contemporary clinical practice. RESULTS: LCH is common in the pediatric population; compared with adults, children usually have a more aggressive clinical course that requires systemic chemotherapy. Patients with low-risk LCH have an excellent prognosis and a long-term survival rate that may be as high as 99%; by contrast, patients with high-risk LCH have a survival rate close to 80%. Typically, adult patients present with limited skin or bone involvement that can be treated with surgical resection or focal radiation therapy, resulting in an overall survival rate of 100%. Smoking cessation can result in the improvement of respiratory symptoms and the spontaneous resolution of pulmonary LCH. Targeted therapy with BRAF inhibitors has been used in select patients with LCH, and the results have been encouraging. CONCLUSIONS: Our understanding of LCH has improved in the last 20 years. Available treatment regimens can control the disease in the majority of patients. The discovery of novel driver mutations and the development of targeted therapy promise better outcomes with fewer long-term therapy-related adverse events, particularly for pediatric and adolescent patients.
BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare histiocytic disorder of unknown etiopathogenesis. Its clinical presentation is variable and ranges from isolated skin or bone disease to a life-threatening multisystem condition. LCH can occur at any age but is more frequent in the pediatric population. A neoplastic origin of this disease has been suggested due to the discovery of the mutually exclusive activating somatic BRAFV600E and MAP2K1 gene mutations that occur in about 75% of patients. METHODS: A survey of recent literature focused on the diagnosis, management, and prognosis of Langerhans cell histiocytosis. Data were collected, analyzed, and discussed with an emphasis on contemporary clinical practice. RESULTS: LCH is common in the pediatric population; compared with adults, children usually have a more aggressive clinical course that requires systemic chemotherapy. Patients with low-risk LCH have an excellent prognosis and a long-term survival rate that may be as high as 99%; by contrast, patients with high-risk LCH have a survival rate close to 80%. Typically, adult patients present with limited skin or bone involvement that can be treated with surgical resection or focal radiation therapy, resulting in an overall survival rate of 100%. Smoking cessation can result in the improvement of respiratory symptoms and the spontaneous resolution of pulmonary LCH. Targeted therapy with BRAF inhibitors has been used in select patients with LCH, and the results have been encouraging. CONCLUSIONS: Our understanding of LCH has improved in the last 20 years. Available treatment regimens can control the disease in the majority of patients. The discovery of novel driver mutations and the development of targeted therapy promise better outcomes with fewer long-term therapy-related adverse events, particularly for pediatric and adolescent patients.