Langerhans Cell Histiocytosis Treatment (PDQ®)

General Information About Langerhans Cell Histiocytosis (LCH)

Langerhans cell histiocytosis (LCH) is a rare disease that occurs when the body makes too many Langerhans cells. A Langerhans cell is a type of white blood cell that helps the body fight infection. Langerhans cells (also called histiocytes) are normally found in the skin, lymph nodes, spleen, bone marrow, and lungs. In LCH, extra Langerhans cells spread through the blood and build up in certain parts of the body, where they can damage tissue or form tumors.

Scientists do not agree on whether LCH is a type of cancer or is a condition caused by a change in the immune system. LCH is often treated with anticancer drugs that may also be used to treat immune system conditions.

LCH may occur at any age, but is most common in young children. The treatment of LCH in children and adults is described in separate sections.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with childhood Langerhans cell histiocytosis. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site.

Anything that increases your risk of getting a disease is called a risk factor. Having a risk factor does not mean that you will get the disease; not having risk factors doesn't mean that you will not get the disease. People who think they may be at risk should discuss this with their doctor. Risk factors for LCH may include the following:

• Having a parent who was exposed to certain chemicals such as benzene.
• Having infections as a newborn.
• Having a family history of thyroid disease.

These and other symptoms may be caused by LCH. Other conditions may cause the same symptoms. A doctor should be consulted if any of the following problems occur:

In infants, signs and symptoms of LCH may include:

• Flaking of the scalp that may look like "cradle cap".
• Raised, brown or purple spots anywhere on the body.

In children and adults, signs and symptoms of LCH may include:

• Flaking of the scalp that may look like dandruff.
• Raised, red or brown, crusted rash in the groin area, abdomen, back or chest.
• Bumps or ulcers behind the ears, on the scalp, or in the groin area.

Signs and symptoms of LCH may include:

• Swollen gums.
• Sores on the roof of the mouth, inside the cheeks, or on the tongue or lips.

Signs and symptoms of LCH may include:

• Swelling or a lump over a bone, such as the skull, hip, ribs, spine, or elbow.
• Pain where there is swelling or a lump over a bone.

Signs and symptoms of LCH may include:

• Swollen lymph nodes.
• Trouble breathing.

Signs and symptoms of LCH may include:

• Diabetes insipidus. This can cause a strong thirst and frequent urination.
• Slow growth.
• Late puberty.

Signs and symptoms of LCH 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 teens, this can also cause behavior problems, weight gain, slowed growth, and late puberty.
• Trouble breathing.

Signs and symptoms of LCH may include:

• Diabetes insipidus. This can cause a strong thirst and frequent urination.
• Trouble breathing.
• Loss of balance, uncoordinated body motions, and trouble walking.
• Trouble speaking.
• Changes in behavior.
• Memory problems.

Signs and symptoms of LCH may include:

• Swelling in the abdomen caused by a build up of extra fluid.
• Yellowing of the skin and whites of the eyes.
• Easy bruising or bleeding.

Signs and symptoms of LCH may include:

• Spontaneous pneumothorax. This can cause chest pain or tightness, trouble breathing, feeling tired, and the skin to turn a bluish color.
• Trouble breathing, especially in adults who smoke.

Signs and symptoms of LCH may include:

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

The following tests and procedures may be used to detect (find) and diagnose LCH or conditions caused by LCH:

• Physical exam and history: An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient's health habits and past illnesses and treatments will also be taken.
• Neurological exam: A series of questions and tests to check the brain, spinal cord, and nerve function. The exam checks a person's mental status, coordination, and ability to walk normally, and how well the muscles, senses, and reflexes work. This may also be called a neuro exam or a neurologic exam.
• 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 in the organ or tissue that makes it.
• 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.
• 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, blood, and a small piece of bone by inserting a hollow needle into the hipbone or breastbone. A pathologist views the bone marrow, blood, and bone under a microscope to look for signs of LCH. Bone marrow aspiration and biopsy. After a small area of skin is numbed, a Jamshidi needle (a long, hollow needle) is inserted into the patient's hip bone. Samples of blood, bone, and bone marrow are removed for examination under a microscope.
• 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 and is detected by a scanner.Bone scan. A small amount of radioactive material is injected into the patient's bloodstream and collects in abnormal cells in the bones. As the patient lies on a table that slides under the scanner, the radioactive material is detected and images are made on a computer screen or film.
• 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.
• 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.Computed tomography (CT) scan of the abdomen. The patient lies on a table that slides through the CT machine, which takes x-ray pictures of the inside of the body.
• 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).Magnetic resonance imaging (MRI) of the abdomen. The patient lies on a table that slides into the MRI machine, which takes pictures of the inside of the body. The pad on the patient's abdomen helps make the pictures clearer.
• Somatostatin receptor scintigraphy: A type of radionuclide scan used to find certain tumors. A small amount of a radioactive drug similar to somatostatin is injected into a vein and travels through the bloodstream. The radioactive drug attaches to tumor cells that have receptors for somatostatin. A radiation-measuring device detects the radioactive drug and makes pictures showing where the tumor cells are in the body. Also called octreotide scan and SRS.
• 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.PET (positron emission tomography) scan. The patient lies on a table that slides through the PET machine. The head rest and white strap help the patient lie still. A small amount of radioactive glucose (sugar) is injected into the patient's vein, and a scanner makes a picture of where the glucose is being used in the body. Cancer cells show up brighter in the picture because they 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.
• Endoscopy: A procedure to look at organs and tissues inside the body to check for abnormal areas. 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 Birbeck granules. Birbeck granules are found in Langerhans cells. To diagnose LCH, a biopsy of bone lesions, skin, lymph nodes, or the liver may be done.

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, bone marrow, or lung is harder to treat and is called "high-risk".

The prognosis (chance of recovery) and treatment options depend on the following:

• Whether the disease is found in one or more places in the body.
• Whether the disease is found in the liver, spleen, lung, bone marrow, or certain bones in the skull.
• How quickly the disease responds to initial treatment.
• Whether the disease has just been diagnosed or has come back (recurred).

In infants up to one year of age, LCH may disappear without treatment.

Stages of LCH

The extent or spread of disease is usually described as stages. There is no staging system for LCH. Before planning treatment, it is important to know whether there is single-site, multiple-site, or multisystem disease and whether "low-risk" organs (skin, bones, lymph nodes, pituitary gland) or "high-risk" organs (spleen, liver, bone marrow, lung) are affected.

LCH may be described as single-site, multiple-site, and multisystem disease.

• Single-site: Occurs in one organ or system in the body such as the skin, mouth, bone, lymph node, thymus, pituitary gland, or central nervous system.
• Multiple-site: Occurs in more than one part of the same organ or area of the body.
• Multisystem: Occurs in two or more organs or areas of the body.

Recurrent LCH

Recurrent Langerhans cell histiocytosis is disease that has recurred (come back) after it has been treated. The disease may come back in the same place or in other parts of the body.

Treatment Option Overview for 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. 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 be enrolled in a clinical trial in order to benefit from advances in LCH treatment and ongoing care.

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

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

• Primary care physician.
• Pediatric surgeon.
• Pediatric hematologist.
• Radiation oncologist.
• Neurologist.
• Endocrinologist.
• Pediatric nurse specialist.
• Rehabilitation specialist.
• Psychologist.
• Social worker.
• Geneticist.

Some treatments cause side effects that continue or appear months or years after treatment has ended. These are called late effects. Late effects of treatment for LCH may include the following:

• Slow growth and development.
• Hearing loss.
• Bone, tooth, liver, and lung problems.
• Changes in mood, feeling, learning, thinking, or memory.
• Risk of cancer related to treatment.

Some late effects may be treated or controlled. It is important to talk with your child's doctors about the possible late effects caused by some treatments.

LCH is usually treated with anticancer treatments. These treatments stop the LCH cells from growing and dividing.

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

Surgery may be used to remove LCH lesions.

Corticosteroids are steroids used to treat LCH lesions.

Chemotherapy is a treatment that uses drugs to stop the growth of cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly onto the skin or into the cerebrospinal fluid, an organ, or a body cavity such as the abdomen, the drugs mainly affect cells in those areas (regional chemotherapy).

Nitrogen mustard is a drug that is applied directly to the skin to treat small LCH lesions.

Photodynamic therapy is a treatment that uses a drug and a certain type of laser light to kill cells. A drug that is not active until it is exposed to light is injected into a vein. The drug collects more in LCH cells than in normal cells. For LCH, laser light is shined onto the skin and the drug becomes active and kills the LCH 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 therapy (PUVA), the patient receives a drug called psoralen and then ultraviolet radiation is directed to the skin.

Radiation therapy is a treatment that uses high-energy x-rays or other types of radiation to kill cells or keep them from growing. External radiation therapy uses a machine outside the body to send radiation toward the LCH lesion.

Information about clinical trials is available from the NCI Web site.

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

Many of today's standard treatments for disease 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 diseases 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.

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

Clinical trials are taking place in many parts of the country. See the Treatment Options for Childhood LCH and the Treatment Options for Adult LCH sections that follow for links to current treatment clinical trials. These have been retrieved from NCI's clinical trials database.

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 and may occur within one year after stopping treatment. Patients with single-site disease are less likely to have a reactivation, while patients with multisystem disease are more likely to have a reactivation. More common sites of reactivation are bone, ears, or skin, and 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 over a number of years.

Some of the tests that were done to diagnose the disease may be repeated. This is to see how well the treatment is working and if new lesions have appeared. These tests may include:

• Physical exam.
• Neurological 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.
• 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.

Decisions about whether to continue, change, or stop treatment may be based on the results of these tests.

Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your condition has changed or if the disease has recurred (come back). These tests are sometimes called follow-up tests or check-ups.

Treatment Options for Childhood LCH

Treatment Options for Single- and Multiple-Site Lesions

Skin Lesions

Treatment of childhood LCH single-site skin lesions may include the following:

• Watchful waiting.
• Steroids or nitrogen mustard applied to the skin.
• Chemotherapy, such as methotrexate or thalidomide, given by mouth.
• Photodynamic therapy with psoralen and ultraviolet A radiation (PUVA).

Bone Lesions

Treatment of childhood LCH single-site bone lesions may include surgery with or without steroid therapy. Treatment of childhood LCH multiple-site bone lesions may include chemotherapy and steroid therapy.

Treatment of childhood LCH single-site bone lesions on the sides of the skull, behind the ears, or around the eyes may include:

• Chemotherapy and steroid therapy.
• Surgery.

Treatment of spine or hip bone lesions that have weakened the bone and may lead to a broken bone in childhood LCH may include:

• Radiation therapy.
• Surgery to strengthen the weakened bone by bracing or fusing the bones together.

Central Nervous System Lesions

Treatment of childhood LCH central nervous system lesions may include chemotherapy.

Multiple-Site Lesions

Treatment of childhood LCH multiple-site lesions (such as two or more single-site bone, skin, lymph node, or pituitary gland lesions) may include chemotherapy and steroid therapy. Treatment of childhood LCH that occurs in "low-risk" organs is about 6 months long.

Treatment of childhood LCH spleen, liver, bone marrow, or lung lesions (with or without skin, bone, lymph node, or pituitary gland lesions) may include chemotherapy and steroid therapy. Treatment of childhood LCH that occurs in "high-risk" organs is about 12 months long.

Treatment Options for Multisystem Lesions

Treatment of childhood LCH multisystem disease lesions may include:

• Chemotherapy with or without steroid therapy.
• A liver transplant for patients with severe liver damage.

Treatment Options for Recurrent, Refractory, and Progressive Childhood LCH

Recurrent LCH is disease that cannot be detected after treatment and then comes back. Treatment of recurrent childhood LCH may include chemotherapy with or without steroid therapy.

Refractory LCH is disease that does not get better with treatment. Treatment of refractory childhood LCH in "high-risk" organs or refractory LCH in multisystem "low-risk" organs may include high-dose chemotherapy with or without stem cell transplant.

Progressive LCH is disease that continues to grow during treatment. Treatment of progressive childhood LCH in patients with multisystem disease may include chemotherapy using anticancer drugs that have not been given to the patient before.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with childhood Langerhans cell histiocytosis. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site.

Treatment Options for Adult LCH

Treatment of LCH in adults is usually the same as for children. (See the Treatment Options for Childhood LCH section above for more information).

Treatment may include:

• Combination chemotherapy with or without steroid therapy.
• Anti-inflammatory drugs combined with chemotherapy.
• A clinical trial of lung transplant for patients with severe lung damage.

For more information about LCH trials for adults, see the Histiocyte Society website.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with adult Langerhans cell histiocytosis. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site.