Castleman Disease

What Is Castleman Disease?

Castleman disease (CD) is a disease of lymph nodes and related tissues. It was first described by Dr. Benjamin Castleman in Boston in 1956. It was previously called "Castleman�s disease." CD is also known as giant lymph node hyperplasia and angiofollicular lymph node hyperplasia.

Although CD is not officially a cancer, the "multicentric" form of this disease acts very much like lymphoma (cancer of lymph nodes). In fact, many people with this disease eventually develop lymphomas. This is why it is included in the American Cancer Society�s cancer information database. (For information about lymphoma, see the American Cancer Society documents, Hodgkin Disease and Non-Hodgkin Lymphoma.) Instead of being called a cancer, CD is often called a lymphoproliferative disorder -- meaning there is an abnormal overgrowth of lymph nodes -- similar in many ways to lymphomas. Like lymphoma, CD is frequently treated with chemotherapy or radiation therapy.

About lymph nodes and lymphoid tissue

Lymphoid tissue, also known as lymphatic tissue, is the main part of the immune system. It is formed by different types of cells that work together to resist infections. Lymphoid tissue also has a role in the body's resistance against some forms of cancer. The main cell of lymphoid tissue is the lymphocyte. There are 2 types of lymphocytes: B cells and T cells.

Lymphoid tissue is found in many places throughout the body, including:

• lymph nodes (bean-sized collections of immune system cells found clustered in the groin and underarm areas, on the sides of the neck, inside the chest, and scattered widely though the body including the abdomen)
• thymus gland (found behind the chest bone and in front of the heart)
• spleen (on the left side of the abdomen next to the stomach)
• tonsils and adenoids
• bone marrow

Types of Castleman disease

The 2 main forms of Castleman disease are localized and multicentric. They affect people very differently.

Localized Castleman disease

Localized or unicentric Castleman disease (CD) only affects a single lymph node and is not widespread. The lymph nodes in the chest and abdomen are affected most often. CD causes these lymph nodes to enlarge. These abnormally large lymph nodes may press on other organs and tissues inside the chest or abdomen. If they are in the abdomen, the person might feel abdominal discomfort. Enlarged lymph nodes in the chest can press on the windpipe (trachea) or smaller breathing tubes (bronchi) causing breathing problems. Sometimes the enlarged lymph nodes are in places such as the neck, groin, or underarms and can be felt easily. People with localized CD disease are usually cured when the lymph node is surgically removed..

Multicentric Castleman disease

Multicentric Castleman disease (CD) affects more than one group of lymph nodes and may also affect other organs containing lymphoid tissue. This form sometimes occurs in people infected with human immunodeficiency virus (HIV), the virus that causes AIDS. Multicentric CD is more serious than the localized type, particularly in people with HIV infection.

People with multicentric CD often have serious infections, fevers, weight loss, fatigue, night sweats, and nerve damage that can cause weakness and numbness. Blood tests often show too few red blood cells (anemia) and high levels of antibodies in the blood (hypergammaglobulinemia). CD can weaken the immune system severely, making it hard to fight infection. Infections in people with multicentric CD can be very serious - even causing death. CD also increases the risk of developing malignant lymphomas, which may be fatal.

Microscopic subtypes of Castleman disease

Castleman disease can also be classified as either a hyaline vascular type or a plasma cell type based on how the lymph node tissue appears under a microscope. Less often, a combination of both types may occur. The hyaline vascular type is more common and tends to be localized, while the plasma cell type tends to be multicentric, but exceptions to this rule often occur. In choosing treatments, doctors consider the microscopic type less important than whether the disease is localized or multicentric.

Do We Know What Causes Castleman Disease?

No one has discovered the cause of this disease, but many doctors suspect a virus is involved. Doctors have found a virus called human herpes virus type 8 (HHV-8) in many people with multicentric Castleman disease (CD). This virus is also known as Kaposi sarcoma--related herpes virus (KSHV), because it has also been found in people with Kaposi sarcoma (formerly called Kaposi�s sarcoma). In fact, some people with CD also have Kaposi sarcoma.

Doctors suspect that problems with the way a patient's immune system is working may contribute to development of CD. Many people with CD have abnormally high blood levels of certain substances produced by immune system cells.

Some scientists believe that CD occurs when there is too much of a protein called interleukin-6 (IL-6). IL-6 is a protein that the body makes to help regulate immune function. Too much IL-6 seems to cause lymphocytes to reproduce excessively. High levels of IL-6 are seen in CD, and tend to be associated most often with multicentric disease. There is a link between HHV-8 and IL-6.

How Is Castleman Disease Treated?

This information represents the views of the doctors and nurses serving on the American Cancer Society's Cancer Information Database Editorial Board. These views are based on their interpretation of studies published in medical journals, as well as their own professional experience.

The treatment information in this document is not official policy of the Society and is not intended as medical advice to replace the expertise and judgment of your cancer care team. It is intended to help you and your family make informed decisions, together with your doctor.

Your doctor may have reasons for suggesting a treatment plan different from these general treatment options. Don't hesitate to ask him or her questions about your treatment options.

Surgery

Surgery is often used to obtain a tissue sample to diagnose Castleman disease. A lymph node biopsy is usually a minor procedure. .

Surgery is also a very effective treatment for localized disease. The type of surgery depends on where the disease is located. If it is in a place that is hard to get to, like deep in the chest or abdomen, the surgeon would then have to cut into the chest or abdomen. These are common procedures, but they can cause pain and people will need to be in the hospital for a few days after the operation. If the involved lymph nodes are easy to get to, such as in the armpit, then surgery is simpler, there is less pain after the operation, and hospitalization may not be needed.

Radiation Therapy

Radiation therapy uses high-energy radiation to kill cells. Radiation focused from a source outside the body is called external beam radiation. Radiation therapy has sometimes been used instead of surgery to effectively treat localized disease.

Side effects of radiation therapy may include mild skin problems or fatigue. Radiation of the abdomen may cause nausea, diarrhea, and loss of appetite. These side effects tend to improve a short while after the radiation is stopped. When radiation therapy is given to the chest, there is a risk of permanent lung damage leading to breathing problems and shortness of breath. Radiation may also make the side effects of chemotherapy worse if they both are given at the same time.

Corticosteroids

Corticosteroids are a group of drugs related to hormones produced by the adrenal glands. These drugs are useful in treating people with certain immune system diseases and cancers that develop from immune system cells, such as lymphomas. Some patients with multicentric Castleman disease benefit from treatment with these drugs.

Corticosteroids are usually taken as pills. Prednisone is the corticosteroid drug most commonly used in these conditions.

Side effects of corticosteroids can include increased blood sugar that may lead to diabetes, depression, reduced resistance to infections, weakened bones, fatigue, muscle weakness, weight gain, fluid retention, and high blood pressure.

Chemotherapy

Chemotherapy is the use of anticancer drugs that are injected into a vein or a muscle or are taken by mouth. These drugs enter the bloodstream and reach all areas of the body, making this treatment very useful for multicentric disease. Chemotherapy may be used alone, in combination with corticosteroids, or in combination with radiation therapy (chemoradiation).

Many drugs have been used to treat patients with Castleman disease (CD). Those used most often include carmustine, cladribine, chlorambucil, cyclophosphamide, doxorubicin, etoposide, melphalan, vinblastine, and vincristine. Often several drugs are combined. Chemotherapy combinations like those used for lymphoma have been used. Depending on the drugs, the treatments are given on different schedules but are usually repeated several times in cycles 3 or 4 weeks apart.

Many chemotherapy treatments are given on an outpatient basis (in the doctor's office or clinic), but some require hospital admission. Sometimes a patient may take one drug combination for several cycles and then later be switched to a different one. Because multicentric CD is so rare, there is not a lot of information on how well chemotherapy works.

Because chemotherapy drugs can damage normal cells, some side effects may occur. These depend on the type and dose of drugs given and the length of time they are taken. Drugs used in chemotherapy attack cells that are rapidly dividing. This means they will also attack some normal tissues such as the bone marrow, the lining of the mouth and intestines, and the hair follicles, which also grow rapidly to replace cells that wear out. As a result, a patient may have:

• hair loss
• mouth sores
• loss of appetite
• nausea and vomiting
• lowered resistance to infection (due to low white blood cell counts)
• easy bruising and bleeding (due to low platelet counts)

These side effects are usually temporary and go away after treatment is finished. Still, doctors try to avoid or minimize them as much as possible. There are ways to lessen these side effects. For example, drugs can be given before or along with chemotherapy to prevent or reduce nausea and vomiting.

Because a low white blood cell count is an important risk factor for serious infections, some patients find it helpful to keep track of their counts. If you are interested in this information ask your doctor or nurse about your blood cell counts and what these numbers mean. You may want to keep a diary of your treatment and blood counts to help you follow the effects of your treatment.

Organs that could be damaged by chemotherapy drugs include the kidneys, liver, testes, ovaries, brain, heart, and lungs. Many of the drugs used to treat Castleman disease (CD) can cause nerve damage, leading to problems such as numbness and tingling in the hands and feet. If serious side effects occur, the chemotherapy may have to be reduced or stopped, at least temporarily. Your doctor will carefully monitor and adjust drug doses because some side effects to organs can be permanent.

Immunotherapy

Monoclonal antibodies

Monoclonal antibodies are special immune proteins made in the lab. They are directed toward specific molecules on the surface of cells. Rituximab (Rituxan^®) is a monoclonal antibody that is widely used for lymphoma. It can also be helpful in treating Castleman disease (CD). Rituximab specifically recognizes and attaches to a protein called CD20 that is found on the surface of some lymphocytes. This attachment tells the cell to die. Patients get rituximab through infusion into a vein (IV) at the oncologist's office or clinic. Side effects are most common during the infusion, and include chills, fever, nausea, rashes, fatigue, and headaches. Unlike regular chemotherapy, rituxan does not cause low blood counts or hair loss.

Immunomodulating agents

Thalidomide: The drug thalidomide is used to treat multiple myeloma, and has helped some patients with CD. Side effects of thalidomide include drowsiness, fatigue, severe constipation, and neuropathy (nerve damage causing pain). There is also an increased risk of serious blood clots (that start in the leg and can travel to the lungs). Because thalidomide causes severe birth defects if taken during pregnancy, this drug can only be obtained through a special program run by the drug company that makes it.

Interferon: Interferon is a hormone-like protein naturally produced by white blood cells to help the immune system fight infections. Some patients with CD disease have improved with interferon treatment. Side effects of this treatment include moderate to severe fatigue, fever, chills, headaches, muscle and joint aches, and mood changes.

Antiviral drugs

Because CD is associated with the HHV-8, doctors have had some success in treating a few patients with multicentric CD with drugs that kill this virus. One drug that has been used is called ganciclovir. Many patients with HIV infection are treated with drugs against the HIV virus (anti-retroviral therapy). The effect of therapy for HIV on CD is not clear.