The following information may help to address your question:
What is Langerhans cell histiocytosis (LCH)?
Langerhans cell histiocytosis (LCH)
is a disorder that primarily affects children, but is also found in adults of all ages. People with LCH produce too many Langerhans cells or histiocytes
, a form of white blood cell
found in healthy people that is supposed to protect the body from infection. In people with LCH, these cells multiply excessively and build up in certain areas of the body, causing tumors
called granulomas to form.
The symptoms of LCH vary from person to person, depending on the areas of the body affected. LCH may be found in many areas of the body, including but not limited to the skin and nails, mouth, bones, lymph nodes
, pituitary gland, and thyroid gland. When it is found in multiple areas of the body, it is known as multisystem disease.
The cause of this disease is unknown, although most data suggest that it is characterized by a growth of immature Langerhans cells that appear to have mutations
of the BRAF gene
in about half the cases. LCH is not caused by a known infection, is not contagious, nor is it believed to be inherited
. There remain differing opinions among experts as to whether it is definitively a cancer
Treatment for LCH varies and may include surgery, chemotherapy
, radiation therapy
, and use of certain medications.
LHC includes four variants, with different degrees of severity:
- Hashimoto-Pritzker disease, a congenital self-healing form
- Letterer-Siwe disease, a severe, acute and disseminate form
- Hand-Schüller-Christian disease, an intermediate chronic form with multiple lesions characterized by diabetes insipidus, bulging of the eye and localized lesions in the bone
- Eosinophilic granuloma, a less severe form, characterized by solitary or few, and chronic lesions of bone or other organs.
Because all the variants have many common symptoms it is thought that they may be manifestations of LCH and not separate syndromes
Last updated: 9/11/2017
What causes Langerhans cell histiocytosis?
The cause of Langerhans cell histiocytosis (LCH) is unknown in many cases.
However, somatic mutations
in the BRAF
gene have been identified in the Langerhans cells of about half of people with LCH. Somatic gene mutations are acquired during a person's lifetime, which means they are acquired after conception and are only present in certain cells. Because they are not present in the germ cells
(egg and sperm), they are not passed on to the next generation (are not inherited).
gene provides instructions for making a protein
that is normally switched on and off in response to signals that control cell growth and development. Somatic mutations cause the BRAF protein in affected cells to be continuously on and to transmit messages to the nucleus
even in the absence of these chemical signals. The overactive protein may contribute to the development of LCH by allowing the Langerhans cells to grow and divide uncontrollably.
The protein produced by the BRAF
gene is part of a signaling pathway known as the RAS/MAPK pathway, which controls several important cell functions. Specifically, the RAS/MAPK pathway regulates the growth and division (proliferation) of cells, the process by which cells mature to carry out specific functions (differentiation), cell movement (migration), and the self-destruction of cells (apoptosis
). Chemical signaling through this pathway is essential for normal development before birth.
gene belongs to a class of genes known as oncogenes
. When mutated, oncogenes have the potential to cause normal cells to become cancerous. Changes in other genes such as the MAP2K
gene (20% of the cases), and other rarer genes (also involved in the RAS/MAPK pathway), have also been identified in the Langerhans cells of some people with LCH. Some researchers believe that additional factors, such as viral infections and environmental toxins
, may also influence the development of this complex disorder.
Family members of LCH patients have a higher incidence of thyroid disease. Smoking is strongly associated with lung LCH.
Last updated: 9/12/2017
Is Langerhans cell histiocytosis inherited?
Although Langerhans cell histiocytosis is generally considered a sporadic, non-hereditary condition, it has reportedly affected more than one individual in a family in a very limited number of cases (particularly identical twins
Last updated: 12/2/2013
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