Langerhans Cell Histiocytosis
Langerhans cell histiocytosis (LCH) is a group of rare disorders all characterized by the overproliferation of Langerhans cells. Treatment for this condition varies and usually includes a combination of chemotherapy, radiation therapy, corticosteroids, and surgery. Some patients may not need any intervention beyond close monitoring.
Normally, Langerhans cells function as part of the immune system and help fight infection, but when Langerhans cells proliferate uncontrollably, they can accumulate in body tissues, causing damage or the formation of a lesion.
LCH can arise anywhere in the body, but is found most often in the bones, including the skull and—very rarely—the spine. Other common locations include the skin, spleen, lungs, liver, and pituitary gland. LCH may appear either as a single lesion or multiple lesions. When LCH involves the central nervous system, disease is usually also found elsewhere in the body. The focus of this page is LCH of the brain and skull.
Rather than referring to a single disorder, LCH describes a spectrum of diseases whose characteristics and relationships continue to be studied. Currently, the LCH designation includes the following subtypes:
- Eosinophilic granuloma: This is the most common subtype and is usually found as single or multiple lesions in the skull but can arise in other bones, such as the vertebrae, ribs, mandibles and bones of the arms and legs.
- Hand-Schüller-Christian disease: This subtype tends to have multiple lesions and is accompanied by diabetes insipidus, exophthalmos, and skull lesions.
- Letterer-Siwe disease: This is the least common but most severe subtype, affecting infants and children younger than age 2. This disease is systemic, involving the whole body, and can be fatal. Symptoms are often most evident on the skin, such as purpuric rash, hemorrhage under the skin and pustules on the skin.
- Hashimoto-Pritzker disease: This is a congenital condition that typically occurs within the first few months of life and then resolves on its own a few months later. Reddish-brown papules on the head, neck, hands, and feet often accompany this disease. The cause of this condition is unclear.
Symptoms vary greatly depending on the location of LCH and subtype involved. Some possible symptoms include bone pain, abdominal pain, swollen gums, mouth ulcers, loosening or loss of teeth, swollen and tender lymph nodes, jaundice, hearing loss, and skin rash. The skin rash may flake on the scalp, resembling cradle cap, or manifest as red or brown blisters.
If LCH is in the skull and/or brain, symptoms can include:
- Vision disturbances
- Cognitive dysfunction
- Changes in behavior
Lesions often involve the pituitary gland and sometimes the nearby hypothalamus too, resulting in endocrine dysfunction. Symptoms that suggest pituitary involvement include diabetes insipidus, characterized by excessive sensation of thirst and frequent urination; failure to thrive; short stature and early or delayed sexual maturation.
Often, a neurological examination is conducted to assess symptoms and identify possible problems. This exam may include assessments of motor function, ability to swallow, hearing, sense of smell, eye movements, sensation, balance. and coordination.
The key component of diagnosis is imaging. X-rays, bone scans, computed tomography (CT) scans or magnetic resonance imaging (MRI) scans may be used to visualize a lesion. CT and MRI scans can be conducted with or without contrast enhancement.
Additional tests may include a water deprivation test to diagnose diabetes insipidus and blood tests to evaluate liver function, acquire a complete blood count or measure hormone levels.
To confirm a diagnosis, biopsy of the lesion is generally required. Also, the tissue sample obtained during the biopsy may be used to detect a BRAF mutation. This information helps guide treatment decisions.
The causes of LCH are not entirely understood, but LCH is associated in some cases with spontaneous mutations in genes that control the MAP Kinase pathway, such as BRAF and MAPK2, which then lead to the accidental triggering of the gene ERK. These mutations are not inherited.
Children of parents who were exposed to benzene have an increased risk for developing LCH.
LCH is very rare, with approximately 1,200 new cases in the United States each year.
Males are two times more likely to have LCH than females.
LCH can arise in adults but is more frequent among young children. Age of onset differs depending on the type of LCH.
- Eosinophilic granuloma is most frequent among children age 5 to 15.
- Hand-Schüller-Christian syndrome is most frequent among children between the ages of 2 and 10.
- Letterer-Siwe disease is most common among children younger than 2 years.
At Columbia, our neurosurgeons use the latest surgical techniques to treat LCH that arises in the brain and skull, providing the best possible outcomes.
Treatment depends on a variety of factors, most especially whether disease is localized to the brain and skull or systemic.
Not all patients will need treatment. For some, close observation is the best plan to follow because the type of LCH they have often resolves on its own. There are other patients whose lesions resolve simply as a result of inserting a biopsy needle.
For those who need treatment, a combination of chemotherapy, radiation therapy, corticosteroids, and surgery is used, and our neurosurgeons devise a treatment plan that is most suited for each patient’s condition.
Surgery is often a simple procedure to excise a single bone lesion in the skull. For lesions in the brain or skull, chemotherapy, radiation therapy, and/or corticosteroids can also be used.
If diabetes insipidus or other endocrine disorders are present, hormone replacement therapy may be needed.