Langerhans cell histiocytosis is a rare disorder that can damage tissue or cause lesions to form in one or more places in the body.

Langerhans cell histiocytosis (LCH) is a rare disease that begins in LCH cells. LCH cells are a type of dendritic cell that normally helps the body fight infection. Sometimes mutations (changes) develop in genes that control how dendritic cells function. These include mutations of the BRAF, MAP2K1, RAS, and ARAF genes. These mutations may cause too many LCH cells to grow and build up in certain parts of the body, where they can damage tissue or form lesions.

It is not known whether LCH is a form of cancer or a cancer-like disease.

Doctors who treat cancer also treat LCH, and sometimes they use cancer therapies to treat this disease. For more information, see the sections on the treatment of LCH in children and the treatment of LCH in adults.

Langerhans cell histiocytosis is a disorder in which excess immune system cells called Langerhans cells build up in the body. Langerhans cells, which help regulate the immune system, are normally found throughout the body, especially in the skin, lymph nodes, spleen, lungs, liver, and bone marrow. In Langerhans cell histiocytosis, excess immature Langerhans cells usually form tumors called granulomas. Many researchers now consider Langerhans cell histiocytosis to be a form of cancer, but this classification remains controversial.

In approximately 80 percent of affected individuals, one or more granulomas develop in the bones, causing pain and swelling. The granulomas, which usually occur in the skull or the long bones of the arms or legs, may cause the bone to fracture.

Granulomas also frequently occur in the skin, appearing as blisters, reddish bumps, or rashes which can be mild to severe. The pituitary gland may also be affected; this gland is located at the base of the brain and produces hormones that control many important body functions. Without hormone supplementation, affected individuals may experience delayed or absent puberty or an inability to have children (infertility). In addition, pituitary gland damage may result in the production of excessive amounts of urine (diabetes insipidus) and dysfunction of another gland called the thyroid. Thyroid dysfunction can affect the rate of chemical reactions in the body (metabolism), body temperature, skin and hair texture, and behavior.

In 15 to 20 percent of cases, Langerhans cell histiocytosis affects the lungs, liver, or blood-forming (hematopoietic) system; damage to these organs and tissues may be life-threatening. Lung involvement, which appears as swelling of the small airways (bronchioles) and blood vessels of the lungs, results in stiffening of the lung tissue, breathing problems, and increased risk of infection. Hematopoietic involvement, which occurs when the Langerhans cells crowd out blood-forming cells in the bone marrow, leads to a general reduction in the number of blood cells (pancytopenia). Pancytopenia results in fatigue due to low numbers of red blood cells (anemia), frequent infections due to low numbers of white blood cells (neutropenia), and clotting problems due to low numbers of platelets (thrombocytopenia).

Other signs and symptoms that may occur in Langerhans cell histiocytosis, depending on which organs and tissues have Langerhans cell deposits, include swollen lymph nodes, abdominal pain, yellowing of the skin and whites of the eyes (jaundice), delayed puberty, protruding eyes, dizziness, irritability, and seizures. About 1 in 50 affected individuals experience deterioration of neurological function (neurodegeneration).

Langerhans cell histiocytosis is often diagnosed in childhood, usually between ages 2 and 3, but can appear at any age. Most individuals with adult-onset Langerhans cell histiocytosis are current or past smokers; in about two-thirds of adult-onset cases the disorder affects only the lungs.

The severity of Langerhans cell histiocytosis, and its signs and symptoms, vary widely among affected individuals. Certain presentations or forms of the disorder were formerly considered to be separate diseases. Older names that were sometimes used for forms of Langerhans cell histiocytosis include eosinophilic granuloma, Hand-Schüller-Christian disease, and Letterer-Siwe disease.

In many people with Langerhans cell histiocytosis, the disorder eventually goes away with appropriate treatment. It may even disappear on its own, especially if the disease occurs only in the skin. However, some complications of the condition, such as diabetes insipidus or other effects of tissue and organ damage, may be permanent.

Family history of cancer or having a parent who was exposed to certain chemicals may increase the risk of LCH.

Anything that increases a person's risk of getting a disease is called a risk factor. Not every child with one or more of these risk factors will develop LCH, and it will develop in some children who don’t have any known risk factors. Talk with your doctor if you think you may be at risk.

Risk factors for LCH may include the following:

• Having a parent who was exposed to certain solvents.
• Having a parent who was exposed to metal, granite, or wood dust in the workplace.
• Having a family history of cancer or LCH.
• Having a personal history or family history of thyroid disease.
• Having infections as a newborn.
• Smoking, especially in young adults.
• Being Hispanic.
• Not being vaccinated as a child.

Somatic mutations in the BRAF gene have been identified in the Langerhans cells of about half of individuals with Langerhans cell histiocytosis. Somatic gene mutations are acquired during a person's lifetime and are present only in certain cells. These changes are not inherited.

The BRAF 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 active and to transmit messages to the nucleus even in the absence of these chemical signals. The overactive protein may contribute to the development of Langerhans cell histiocytosis by allowing the Langerhans cells to grow and divide uncontrollably.

Changes in other genes have also been identified in the Langerhans cells of some individuals with Langerhans cell histiocytosis. Some researchers believe that additional factors, such as viral infections and environmental toxins, may also influence the development of this complex disorder.

Normal Function

The BRAF gene provides instructions for making a protein that helps transmit chemical signals from outside the cell to the cell's nucleus. This protein 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.

The BRAF gene belongs to a class of genes known as oncogenes. When mutated, oncogenes have the potential to cause normal cells to become cancerous.

Health Conditions Related to Genetic Changes

Cardiofaciocutaneous syndrome

Mutations in the BRAF gene are the most common cause of cardiofaciocutaneous syndrome. This condition affects many parts of the body, particularly the heart (cardio-), facial features (facio-), and the skin and hair (cutaneous). At least 49 BRAF mutations have been identified in people with this disorder. These mutations change single protein building blocks (amino acids) in the BRAF protein. Almost all of these genetic changes abnormally activate the protein, which disrupts the tightly regulated RAS/MAPK signaling pathway in cells throughout the body. The altered signaling interferes with the normal development of many organs and tissues, resulting in the characteristic features of cardiofaciocutaneous syndrome.

Erdheim-Chester disease

At least one mutation in the BRAF gene has been identified in some people with Erdheim-Chester disease. This rare condition is characterized by the abnormal production and accumulation of immune system cells called histiocytes in many of the body's tissues. The disease most commonly affects the bones, causing bone thickening and pain, but the accumulation of histiocytes can also cause signs and symptoms affecting the brain, eyes, lungs, liver, kidneys, and other organs.

The BRAF gene mutation that causes this condition is somatic, meaning that it occurs during a person's lifetime and is present only in certain cells. The mutation affects a single amino acid in the BRAF protein. Specifically, the mutation replaces the amino acid valine with the amino acid glutamic acid at position 600 (written as Val600Glu or V600E). This mutation leads to production of a BRAF protein that is abnormally active, which disrupts regulation of cell proliferation and may allow histiocytes to grow and divide uncontrollably, leading to the abnormal accumulation of histiocytes that occurs in Erdheim-Chester disease.

Giant congenital melanocytic nevus

The V600E mutation (described above) in the BRAF gene has also been found to cause giant congenital melanocytic nevus. This condition is characterized by a large, noncancerous patch of abnormally dark skin that is present from birth and an increased risk of a type of skin cell cancer called melanoma (described below). In giant congenital melanocytic nevus, a somatic V600E mutation occurs during embryonic development in cells that will develop into pigment-producing skin cells (melanocytes). This mutation leads to production of a BRAF protein that is abnormally active, which disrupts regulation of cell proliferation. The unregulated cell proliferation of early melanocytes leads to a large patch of darkly pigmented skin characteristic of giant congenital melanocytic nevus. Additional gene mutations in cells within the nevus after birth can lead to melanoma in people with giant congenital melanocytic nevus.

Noonan syndrome

MedlinePlus Genetics provides information about Noonan syndrome

Noonan syndrome with multiple lentigines

At least two mutations in the BRAF gene have been found to cause Noonan syndrome with multiple lentigines (formerly called LEOPARD syndrome). This condition is characterized by multiple brown skin spots (lentigines), heart defects, short stature, a sunken or protruding chest, and distinctive facial features. The BRAF gene mutations change single amino acids in the BRAF protein: One mutation replaces the amino acid threonine with the amino acid proline at position 241 (written as Thr241Pro or T241P) and the other mutation replaces the amino acid leucine with the amino acid phenylalanine at position 245 (written as Leu245Phe or L245F).

The BRAF gene changes that cause Noonan syndrome with multiple lentigines are believed to abnormally activate the BRAF protein, which disrupts the regulation of the RAS/MAPK signaling pathway that controls cell functions such as proliferation. This misregulation can result in the various features of Noonan syndrome with multiple lentigines.

Cholangiocarcinoma

MedlinePlus Genetics provides information about Cholangiocarcinoma

Gastrointestinal stromal tumor

MedlinePlus Genetics provides information about Gastrointestinal stromal tumor

Langerhans cell histiocytosis

Somatic mutations in the BRAF gene, most frequently the V600E mutation (described above), have been identified in some individuals with Langerhans cell histiocytosis. This disorder causes an abnormal accumulation of certain immune cells called Langerhans cells in multiple tissues and organs, which often leads to the formation of tumors called granulomas. Many researchers consider Langerhans cell histiocytosis to be a form of cancer, but this classification is controversial.

The BRAF gene mutations, which are found only in the abnormal Langerhans cells, cause the BRAF protein to be continuously active. The overactive protein may contribute to the development of Langerhans cell histiocytosis by allowing the Langerhans cells to grow and divide uncontrollably.

In some other forms of histiocytosis such as Erdheim-Chester disease (described above), the histiocytes do not include Langerhans cells; a disorder of that type is classified as a non-Langerhans cell histiocytosis. It is not clear why the V600E mutation can cause different forms of histiocytosis.

Lung cancer

MedlinePlus Genetics provides information about Lung cancer

Melanoma

The V600E mutation (described above) in the BRAF gene has also been found in about half of noninherited (sporadic) cases of melanoma. Melanoma is a type of skin cancer that begins in pigment-producing cells called melanocytes. In this cancer, a somatic V600E mutation occurs during a person's lifetime, likely caused by ultraviolet (UV) radiation from the sun or other environmental risk factors. This mutation often leads only to the formation of a noncancerous mole. At least one additional mutation is necessary for the development of melanoma.

Multiple myeloma

MedlinePlus Genetics provides information about Multiple myeloma

Cancers

Somatic mutations in the BRAF gene are common in several types of cancer. Normally, the BRAF protein is switched on and off in response to signals that control cell growth and development. Somatic mutations cause the BRAF protein to be continuously active and to transmit messages to the nucleus even in the absence of these chemical signals. The overactive protein may contribute to the growth of cancers by allowing abnormal cells to grow and divide without external signals.

The V600E mutation (described above) is the most common BRAF gene mutation found in human cancers. This mutation has frequently been found in cancers of the colon and rectum, ovary, and thyroid gland. Several other somatic mutations in the BRAF gene have also been associated with cancer.

Other Names for This Gene

• 94 kDa B-raf protein
• B-raf 1
• B-Raf proto-oncogene serine/threonine-protein kinase
• BRAF1
• BRAF1_HUMAN
• Murine sarcoma viral (v-raf) oncogene homolog B1
• p94
• RAFB1
• v-raf murine sarcoma viral oncogene homolog B

Genomic Location

The signs and symptoms of LCH depend on where it is in the body.

These and other signs and symptoms may be caused by LCH or by other conditions. Check with your doctor if you or your child have any of the following:

Bone

Signs or symptoms of LCH that affects the bone may include:

• Swelling or a lump over a bone, such as the skull, jawbone, ribs, pelvis, spine, thigh bone, upper arm bone, elbow, eye socket, or bones around the ear.
• Pain where there is swelling or a lump over a bone.

Children with LCH lesions in bones around the ears or eyes have a high risk of diabetes insipidus and other central nervous system diseases.

Skin and nails

LCH in infants may affect the skin only. In some cases, skin-only LCH may get worse over weeks or months and become a form called high-risk multisystem LCH.

In infants, signs or symptoms of LCH that affects the skin may include:

• Flaking of the scalp that may look like “cradle cap.”
• Flaking in the creases of the body, such as the inner elbow or perineum.
• Raised skin rash with brown or purple areas that occur anywhere on the body.

In children and adults, signs or symptoms of LCH that affects the skin and nails may include:

• Flaking of the scalp that may look like dandruff.
• Raised skin rash with red, brown, or crusted areas that may be itchy or painful. The rash can occur in the groin area or on the abdomen, back, or chest.
• Bumps or ulcers on the scalp.
• Ulcers behind the ears, under the breasts, or in the groin area.
• Fingernails that fall off or have discolored grooves that run across the nail.

Mouth

Signs or symptoms of LCH that affects the mouth may include:

• Swollen gums.
• Sores on the roof of the mouth, inside the cheeks, or on the tongue or lips.
• Teeth that become uneven or fall out.

Lymph nodes and thymus

Signs or symptoms of LCH that affects the lymph nodes or thymus may include:

• Swollen lymph nodes.
• Cough, trouble breathing, or fast breathing.
• Superior vena cava syndrome. This can cause coughing, trouble breathing, and swelling of the face, neck, and upper arms. For more information, see Cardiopulmonary Syndromes.

Endocrine system

Signs or symptoms of LCH that affects the pituitary gland may include:

• Diabetes insipidus. This can cause a strong thirst and frequent urination.
• Slow growth.
• Early or late puberty.
• Being very overweight.

Signs or symptoms of LCH that affects the thyroid may include:

• Swollen thyroid gland.
• Hypothyroidism. This can cause tiredness, lack of energy, being sensitive to cold, constipation, dry skin, thinning hair, memory problems, trouble concentrating, and depression. In infants, this can also cause a loss of appetite and choking on food. In children and adolescents, this can cause behavior problems, weight gain, slow growth, and late puberty.
• Trouble breathing.

Eye

Signs or symptoms of LCH that affects the eye may include:

• Vision problems or blindness.

Central nervous system (CNS)

Signs or symptoms of LCH that affects the CNS (brain and spinal cord) may include:

• Loss of balance, uncoordinated body movements, and trouble walking.
• Trouble speaking.
• Trouble seeing.
• Headaches.
• Changes in behavior or personality.
• Memory problems.

These signs and symptoms may be caused by lesions in the CNS or by CNS neurodegenerative syndrome.

Liver and spleen

Signs or symptoms of LCH that affects the liver or spleen may include:

• Swelling in the abdomen caused by a buildup of extra fluid.
• Trouble breathing.
• Yellowing of the skin and whites of the eyes.
• Itching.
• Easy bruising or bleeding.
• Feeling very tired.
• Diarrhea.
• Bloody stools.

Lung

Signs or symptoms of LCH that affects the lung may include:

• Collapsed lung. This condition can cause chest pain or tightness, trouble breathing, feeling tired, and a bluish color to the skin.
• Trouble breathing, especially in adults who smoke.
• Dry cough.
• Chest pain.

Bone marrow

Signs or symptoms of LCH that affects the bone marrow may include:

• Easy bruising or bleeding.
• Fever.
• Frequent infections.

Tests that examine the organs and body systems where LCH may occur are used to diagnose LCH.

In addition to asking about your health history and doing a physical exam, your doctor may perform the following tests and procedures to diagnose LCH or conditions caused by LCH:

• Complete blood count (CBC) with differential: A procedure in which a sample of blood is drawn and checked for the following:
  • The amount of hemoglobin (the protein that carries oxygen) in the red blood cells.
  • The portion of the blood sample made up of red blood cells.
  • The number and type of white blood cells.
  • The number of red blood cells and platelets.
• Blood chemistry studies: A procedure in which a blood sample is checked to measure the amounts of certain substances released into the body by organs and tissues in the body. An unusual (higher or lower than normal) amount of a substance can be a sign of disease.
• Liver function test: A blood test to measure the blood levels of certain substances released by the liver. A high or low level of these substances can be a sign of disease in the liver.
• BRAF gene testing: A laboratory test in which a sample of blood or tissue is tested for certain mutations in the BRAF gene.
• Urinalysis: A test to check the color of urine and its contents, such as sugar, protein, red blood cells, and white blood cells.
• Water deprivation test: A test to check how much urine is made and whether it becomes concentrated when little or no water is given. This test is used to diagnose diabetes insipidus, which may be caused by LCH.
• Bone marrow aspiration and biopsy: The removal of bone marrow and a small piece of bone by inserting a hollow needle into the hipbone. A pathologist views the bone marrow and bone under a microscope to look for signs of LCH.

  The following test may be done on the tissue that was removed:

  • Immunohistochemistry: A laboratory test that uses antibodies to check for certain antigens (markers) in a sample of a patient’s tissue. The antibodies are usually linked to an enzyme or a fluorescent dye. After the antibodies bind to a specific antigen in the tissue sample, the enzyme or dye is activated, and the antigen can then be seen under a microscope. This type of test is used to help diagnose cancer and to help tell one type of cancer from another type of cancer.
• Bone scan: A procedure to check if there are rapidly dividing cells in the bone. A very small amount of radioactive material is injected into a vein and travels through the bloodstream. The radioactive material collects in the bones with LCH and is detected by a scanner.

• X-ray: An x-ray of the organs and bones inside the body. An x-ray is a type of energy beam that can go through the body and onto film, making a picture of areas inside the body. Sometimes a skeletal survey is done. This is a procedure to x-ray all the bones in the body.
• CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.

• MRI (magnetic resonance imaging): A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. A substance called gadolinium may be injected into a vein. The gadolinium collects around the LCH cells so that they show up brighter in the picture. This procedure is also called nuclear magnetic resonance imaging (NMRI).

• PET scan (positron emission tomography scan): A procedure to find tumor cells in the body. A small amount of radioactive glucose (sugar) is injected into a vein. The PET scanner rotates around the body and makes a picture of where glucose is being used in the body. Tumor cells show up brighter in the picture because they are more active and take up more glucose than normal cells do.

• Ultrasound exam: A procedure in which high-energy sound waves (ultrasound) are bounced off internal tissues or organs and make echoes. The echoes form a picture of body tissues called a sonogram. The picture can be printed to be looked at later.

• Pulmonary function test (PFT): A test to see how well the lungs are working. It measures how much air the lungs can hold and how quickly air moves into and out of the lungs. It also measures how much oxygen is used and how much carbon dioxide is given off during breathing. This is also called lung function test.
• Bronchoscopy: A procedure to look inside the trachea and large airways in the lung for abnormal areas. A bronchoscope is inserted through the nose or mouth into the trachea and lungs. A bronchoscope is a thin, tube-like instrument with a light and a lens for viewing. It may also have a tool to remove tissue samples, which are checked under a microscope for signs of LCH.
• Endoscopy: A procedure to look at organs and tissues inside the body to check for abnormal areas in the gastrointestinal tract or lungs. An endoscope is inserted through an incision (cut) in the skin or opening in the body, such as the mouth. An endoscope is a thin, tube-like instrument with a light and a lens for viewing. It may also have a tool to remove tissue or lymph node samples, which are checked under a microscope for signs of disease.
• Biopsy: The removal of cells or tissues so they can be viewed under a microscope by a pathologist to check for LCH cells. To diagnose LCH, a biopsy of bone, skin, lymph nodes, liver, or other sites of disease may be done.

KEY POINTS

• There is no standard staging system for Langerhans cell histiocytosis (LCH).
• Treatment of LCH is based on where LCH cells are found in the body and whether the LCH is low risk or high risk.
• Sometimes LCH continues to grow or comes back after treatment.

There is no standard staging system for Langerhans cell histiocytosis (LCH).

The process used to find out if cancer has spread to other parts of the body is called staging. There is no standard staging system for LCH.

Treatment of LCH is based on where LCH cells are found in the body and whether the LCH is low risk or high risk.

LCH is described as single-system disease or multisystem disease, depending on how many body systems are affected:

• Single-system LCH: LCH is found in one part of an organ or body system or in more than one part of that organ or body system. Bone is the most common single place for LCH to be found.
• Multisystem LCH: LCH is found in two or more organs or body systems or may be found throughout the body. Multisystem LCH is less common than single-system LCH.

LCH may affect low-risk organs or high-risk organs:

• Low-risk organs include the skin, bone, lungs, lymph nodes, gastrointestinal tract, pituitary gland, thyroid gland, thymus, and central nervous system (CNS).
• High-risk organs include the liver, spleen, and bone marrow.

Sometimes LCH continues to grow or comes back after treatment.

Progressive LCH describes LCH that continues to grow, spread, or get worse. Progressive disease may be a sign that the LCH has become refractory to treatment.

Refractory LCH describes LCH that does not respond to initial treatment.

Recurrent or reactivated LCH describes LCH that has come back after it has been treated.

Many patients with LCH get better with treatment. However, when treatment stops, new lesions may appear or old lesions may come back. This is called reactivation (recurrence) and may occur within 1 year after stopping treatment. Patients with multisystem disease are more likely to have a reactivation. Common sites of reactivation are bone, ears, or skin. Diabetes insipidus also may develop. Less common sites of reactivation include lymph nodes, bone marrow, spleen, liver, or lung. Some patients may have more than one reactivation.

KEY POINTS

• There are different types of treatment for patients with Langerhans cell histiocytosis (LCH).
• Children with LCH should have their treatment planned by a team of health care providers who are experts in treating childhood cancer or LCH.
• Nine types of standard treatment are used to treat LCH.
  • Chemotherapy
  • Surgery
  • Radiation therapy
  • Photodynamic therapy
  • Immunotherapy
  • Targeted therapy
  • Other drug therapy
  • Stem cell transplant
  • Observation
• New types of treatment are being tested in clinical trials.
• Treatment for Langerhans cell histiocytosis may cause side effects.
• Patients may want to think about taking part in a clinical trial.
• Patients can enter clinical trials before, during, or after starting their treatment.
• Follow-up tests may be needed.

There are different types of treatment for patients with Langerhans cell histiocytosis (LCH).

Different types of treatments are available for patients with LCH. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment. Whenever possible, patients should take part in a clinical trial in order to receive new types of treatment for LCH. Some clinical trials are open only to patients who have not started treatment.

Clinical trials are taking place in many parts of the country. Information about ongoing clinical trials is available from the NCI website. Choosing the most appropriate treatment is a decision that ideally involves the patient, family, and health care team.

Children with LCH should have their treatment planned by a team of health care providers who are experts in treating childhood cancer or LCH.

Treatment will be overseen by a pediatric oncologist, a doctor who specializes in treating children with cancer. The pediatric oncologist works with other pediatric healthcare providers who are experts in treating children with LCH and who specialize in certain areas of medicine. These may include the following specialists:

• Pediatrician.
• Pediatric surgeon.
• Pediatric hematologist.
• Radiation oncologist.
• Neurologist.
• Endocrinologist.
• Pediatric nurse specialist.
• Rehabilitation specialist.
• Psychologist.
• Social worker.

Nine types of standard treatment are used to treat LCH.

Although it is unknown whether LCH is a type of cancer, some of the treatments used for cancer are effective at treating LCH.

Chemotherapy

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Chemotherapy that is taken by mouth or injected into a vein or muscle enters the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). Chemotherapy may also be applied to the skin in a cream or lotion (topical chemotherapy).

Chemotherapy may be given by injection, by mouth, or applied to the skin to treat LCH.

Surgery

Surgery may be used to remove LCH lesions and a small amount of nearby healthy tissue. Curettage is a type of surgery that uses a curette (a sharp, spoon-shaped tool) to scrape LCH cells from bone.

When there is severe liver or lung damage, the entire organ may be removed and replaced with a healthy liver or lung from a donor.

Radiation therapy

Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. External radiation therapy uses a machine outside the body to send radiation toward the area of the body with cancer. Ultraviolet B (UVB) radiation therapy may be given using a special lamp that directs radiation toward LCH skin lesions.

Photodynamic therapy

Photodynamic therapy is a cancer treatment that uses a drug and a certain type of laser light to kill cancer cells. A drug that is not active until it is exposed to light is injected into a vein. The drug collects more in cancer cells than in normal cells. For LCH, laser light is aimed at the skin and the drug becomes active and kills the cancer cells. Photodynamic therapy causes little damage to healthy tissue. Patients who have photodynamic therapy should not spend too much time in the sun.

In one type of photodynamic therapy, called psoralen and ultraviolet A (PUVA) therapy, the patient receives a drug called psoralen and then ultraviolet A radiation is directed to the skin.

Immunotherapy

Immunotherapy is a treatment that uses the patient’s immune system to fight cancer. Substances made by the body or made in a laboratory are used to boost, direct, or restore the body’s natural defenses against cancer. Thalidomide is a type of immunotherapy used to treat LCH.

Targeted therapy

Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells. There are different types of targeted therapy:

• BRAF inhibitors block proteins needed for cell growth and may kill cancer cells. The BRAF gene is found in a mutated (changed) form in some LCH and blocking it may help keep LCH cells from growing.
  • Vemurafenib and dabrafenib are BRAF inhibitors used to treat LCH.
  • Trametinib is a BRAF inhibitor that is being studied in the treatment of certain childhood tumors for use alone or combined with dabrafenib.
• Monoclonal antibodies are immune system proteins made in the laboratory to treat many diseases, including cancer. As a cancer treatment, these antibodies can attach to a specific target on cancer cells or other cells that may help cancer cells grow. The antibodies are able to then kill the cancer cells, block their growth, or keep them from spreading. Monoclonal antibodies are given by infusion. They may be used alone or to carry drugs, toxins, or radioactive material directly to cancer cells.
  • Rituximab is a monoclonal antibody used to treat LCH.

Other drug therapy

Other drugs used to treat LCH include the following:

• Steroid therapy, such as prednisone, is used to treat LCH lesions.
• Bisphosphonate therapy (such as pamidronate, zoledronate, or alendronate) is used to treat LCH lesions of the bone and to lessen bone pain.
• Anti-inflammatory drugs are drugs (such as pioglitazone and rofecoxib) that are commonly used to decrease fever, swelling, pain, and redness. Anti-inflammatory drugs and chemotherapy may be given together to treat adults with bone LCH.

Stem cell transplant

Chemotherapy is given to kill cancer cells. Healthy cells, including blood-forming cells, are destroyed by the LCH treatment. Stem cell transplant is a treatment to replace the blood-forming cells. Stem cells (immature blood cells) are removed from the blood or bone marrow of the patient or a donor and are frozen and stored. After the patient completes chemotherapy, the stored stem cells are thawed and given back to the patient through an infusion. These stem cells grow into (and restore) the body's blood cells.

Observation

Observation is closely monitoring a patient's condition without giving any treatment until signs or symptoms appear or change.

New types of treatment are being tested in clinical trials.

Information about clinical trials is available from the NCI website.

Treatment for Langerhans cell histiocytosis may cause side effects.

For information about side effects that begin during treatment for cancer, see our Side Effects page.

Side effects from cancer treatment that begin after treatment and continue for months or years are called late effects. Late effects of cancer treatment may include the following:

• Slow growth and development.
• Hormone imbalance.
• Hearing loss.
• Bone, tooth, liver, and lung problems.
• Changes in mood, feeling, behavior, learning, thinking, or memory.
• Second cancers, such as leukemia, lymphoma, retinoblastoma, Ewing sarcoma, brain or liver cancer.

Some late effects may be treated or controlled. It is important to talk with your child's doctors about the effects cancer treatment can have on your child.

Many patients with multisystem LCH have late effects caused by treatment or by the disease itself. These patients often have long-term health problems that affect their quality of life.

Patients may want to think about taking part in a clinical trial.

For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.

Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.

Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.

Patients can enter clinical trials before, during, or after starting their treatment.

Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment.

Follow-up tests may be needed.

LCH patients should be monitored for many years because of the risk of reactivation (recurrence). Some of the tests that were done to diagnose LCH may be repeated. This is to see how well the treatment is working and if there are any new lesions. These tests may include:

• Physical exam.
• Neurological exam.
• Ultrasound exam.
• MRI.
• CT scan.
• PET scan.

Other tests that may be needed include:

• Brain stem auditory evoked response (BAER) test: A test that measures the brain's response to clicking sounds or certain tones to detect some types of hearing loss.
• Pulmonary function test (PFT): A test to see how well the lungs are working. It measures how much air the lungs can hold and how quickly air moves into and out of the lungs. It also measures how much oxygen is used and how much carbon dioxide is given off during breathing. This is also called a lung function test.
• Chest x-ray: An x-ray of the organs and bones inside the chest. An x-ray is a type of energy beam that can go through the body and onto film, making a picture of areas inside the body.

The results of these tests can show if your condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests.

Certain factors affect prognosis (chance of recovery) and treatment options.

LCH in organs such as the skin, bones, lymph nodes, or pituitary gland usually gets better with treatment and is called "low-risk." LCH in the spleen, liver, or bone marrow is harder to treat and is called "high-risk." Children with LCH in high-risk organs and the gastrointestinal tract have a greater risk of not responding to treatment than patients with high-risk LCH and no disease in the gastrointestinal tract. High-risk LCH is usually seen in children younger than 2 years.

The prognosis and treatment options depend on the following:

• Which organs or body systems are affected by LCH.
• How many organs or body systems the LCH affects.
• Whether LCH is found in the liver, spleen, bone marrow, or certain bones in the skull.
• How quickly LCH responds to initial treatment.
• Whether there are certain mutations in the BRAF gene.
• Whether LCH has just been diagnosed or has come back (recurred).

In infants up to 1 year of age, LCH may go away without treatment.