Castleman disease (CD) is a rare disease of lymph nodes and related tissues.It was first described by Dr. Benjamin Castleman in the 1950s. It is also known as Castleman’s disease, giant lymph node hyperplasia, and angiofollicular lymph node hyperplasia (AFH). CD is not cancer. Instead, it is called a lymphoproliferative disorder. This means there is an abnormal overgrowth of cells of the lymph system that is similar in many ways to lymphomas (cancers of lymph nodes).

Even though CD is not officially a cancer, one form of this disease (known as multicentric Castleman disease) acts very much like lymphoma. In fact, many people with this disease eventually develop lymphomas. And like lymphoma, CD is often treated with chemotherapy or radiation therapy. This is why it is included in the American Cancer Society’s cancer information. (For information about lymphoma, see Hodgkin Disease and Non-Hodgkin Lymphoma.).

About lymph nodes and lymphoid tissue

To understand Castleman disease, it helps to know about the body’s lymph system.

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 help the body fight infections. The main cells in lymphoid tissue are lymphocytes, a type of white blood cell. There are 2 main 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 lymphocytes found in small groups throughout the body, including inside the chest, abdomen, and pelvis. They can sometimes be felt under the skin in the neck, under the arms, and in the groin.
• Thymus: a small organ behind the upper part of the breastbone and in front of the heart. The thymus plays a vital role in development of T cells.
• Spleen: an organ under the lower part of the rib cage on the left side of the body. The spleen makes lymphocytes and other immune system cells to help fight infection. It also stores healthy blood cells and helps filter the blood.
• Tonsils and adenoids: collections of lymphoid tissue at the back of the throat. They help protect the body against germs that are breathed in or swallowed.
• Bone marrow: the soft inner part of certain bones that makes red blood cells, blood platelets, and white blood cells (including lymphocytes).
• Digestive tract: the stomach, intestines, and other organs, which also have lymphoid tissue.

Types of Castleman disease

Doctors can group CD in a number of ways, and they are still trying to determine which classification (or combination of them) provides the most helpful information.

CD is classified by on how much of the body it affects. The main forms of CD are called localized and multicentric. They affect people very differently.

Localized (unicentric) Castleman disease

This is the more common type of CD. Localized CD only affects a single group of lymph nodes. It is not widespread. Lymph nodes in the chest or abdomen are affected most often. CD causes these lymph nodes to grow.

Enlarged lymph nodes in the chest can press on the windpipe (trachea) or smaller breathing tubes going into the lungs (bronchi), causing breathing problems. If the enlarged nodes are in the abdomen, the person might have pain, a feeling of fullness, or trouble eating. Sometimes the enlarged nodes are in places such as the neck, groin, or underarm area and are first noticed as a lump under the skin.

People with localized CD are usually cured when the affected lymph nodes are removed with surgery.

Multicentric Castleman disease

Multicentric Castleman disease (MCD) affects more than one group of lymph nodes. It can 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. You can read more about HIV infection in HIV, AIDS, and Cancer.

People with MCD often have problems such as 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).

MCD can weaken the body’s immune system, making it hard to fight infection. Infections in people with MCD can be very serious, even life threatening. MCD also increases the risk of developing lymphoma, a cancer of lymphoid tissue, which can often be hard to treat.

Microscopic subtypes of CD

Castleman disease can also be classified based on how the lymph node tissue looks under a microscope. These are called microscopic subtypes.

• The hyaline vascular type is most common. It tends to be localized, in which case people often have few symptoms and usually have a good outlook, but in rare cases it can be multicentric.
• The plasma cell type is more likely to cause symptoms and to be multicentric, but it is sometimes localized.
• The mixed subtype shows areas of both hyaline vascular and plasma cell types. It occurs less often.
• The plasmablastic type was recognized more recently. Like the plasma cell type, it is usually multicentric, usually causes symptoms, and has a less favorable outlook.

In choosing treatments, doctors believe that the microscopic type is less important than whether the disease is localized or multicentric.

Subtypes of CD based on viral infections

Infection with certain viruses plays a role in at least some cases of CD.

Multicentric CD is more common in people infected with HIV, the virus that causes AIDS. Doctors sometimes group patients with multicentric CD into those who are infected with HIV (HIV positive) and those who are not infected (HIV negative).

In recent years, it’s become clear that another virus, known as human herpesvirus-8 (HHV-8) or Kaposi sarcoma herpesvirus (KSHV), is often found in the lymph node cells of people with multicentric CD. In fact, HHV-8 is found in the lymph nodes of nearly all CD patients who are HIV positive. Some doctors have suggested classifying CD based on whether the cells contain HHV-8.

After someone is diagnosed with cancer, doctors will try to figure out if it has spread and if so, how far. This process is called staging. The stage of a cancer describes how much cancer is in the body. It helps determine how serious the cancer is and how best to treat it. Doctors also use a cancer's stage when talking about survival statistics.

Since Castleman disease (CD) is not a cancer, it doesn’t have a formal staging system. Instead, doctors use other important pieces of information to help decide on the best treatment and to give them an idea of how well a patient might do.

The most important factor when deciding on treatment is whether the CD is localized/unicentric or multicentric. Localized/unicentric CD affects only a single lymph node (or lymph node group). The multicentric type affects 2 or more groups of lymph nodes in different parts of the body. It may also affect organs like the spleen or liver. Tests are done to see what lymph nodes and organs are affected to learn which type of CD a patient has. Doctors use the results of physical exams and imaging, such as a chest x-ray and either a CT scan or MRI of the chest and abdomen. These are described in Tests for Castleman Disease.

Another factor is the microscopic subtype of the CD, which is a description of the patterns of cells seen under the microscope in the biopsy sample. These subtypes are described in What Is Castleman Disease?

A third important factor is whether or not the patient is infected with the human immunodeficiency virus (HIV), the virus that causes AIDS. Just about all people infected with HIV who develop CD will have the multicentric form of the disease.

Castleman disease (CD) can cause a lot of different types of symptoms, and in some people it might not cause any symptoms at all. If symptoms do occur, they are often like those seen with other diseases, such as infections, autoimmune diseases, or even some types of cancer. Because of this, doctors might not suspect CD at first.

Common symptoms of localized CD

In the localized form of CD, symptoms are found in a particular part of the body. Localized CD often starts as an enlarged lymph node. If the node is just under the skin, such as in the neck or underarm area, it might be seen or felt as a lump. But if it’s in the chest or abdomen (belly), it might not be noticed until it grows large enough to cause other symptoms:

• An enlarged node in the chest might press on the windpipe, which could cause trouble breathing, wheezing, a cough, or a feeling of fullness in the chest.
• An enlarged node in the abdomen can cause trouble eating, pain, or just a feeling of fullness.

In general, most people with localized CD feel well otherwise. In fact, some people have no symptoms at all, and CD is found only when the doctor does a test for another reason. On the other hand, some people with localized CD can also have some of the other symptoms listed below.

Common symptoms of multicentric CD

People with multicentric CD have more than one area of enlarged lymph nodes. The enlarged nodes can be in the chest or abdomen, but multicentric CD often affects lymph nodes in the groin, the underarm area, and on the sides of the neck, which can often be seen or felt as lumps under the skin.

Multicentric CD can also affect lymphoid tissue of internal organs, causing the liver, spleen, or other organs to enlarge. Enlarged organs might be seen or felt as masses under either side of the rib cage. They can also cause problems eating or a sense of fullness (or even pain) in the abdomen.

Other symptoms of CD

In addition, people with either type of CD can have other symptoms (although these symptoms are much more common in people with multicentric CD):

• Fever
• Night sweats (that soak the sheets)
• Weight loss
• Loss of appetite
• Weakness
• Fatigue (tiredness)
• Shortness of breath
• Nausea and vomiting
• Nerve damage that leads to numbness and weakness (neuropathy)
• Leg swelling (edema)
• Skin rashes

Some of these symptoms might come and go over time.

Amyloidosis, a condition where abnormal proteins build up in body tissues, can occur in CD. This can lead to kidney damage, heart damage, nerve damage, and intestinal problems, mainly diarrhea. If CD is treated successfully, the amyloidosis may improve or even go away.

Anemia (having too few red blood cells) is very common in multicentric CD, and can lead to problems such as fatigue and shortness of breath.

CD is rare, and the symptoms above often have other causes. Still, if you have any of these symptoms and they don’t go away within a few weeks (or they get worse), see a doctor so that the cause can be found and treated, if needed.

We aren't sure how many people are diagnosed with Castleman disease (CD) each year. The National Cancer Institute keeps track of how many people have each type of cancer, but because CD is not a cancer it is not included. We do know that CD is rare, especially in people who are otherwise healthy. Recent studies that looked at medical records of patients with CD suggest there may be about 4,300 to 5,100 new cases of CD per year in the US.

• The localized (unicentric) form of CD is more common than the multicentric form (MCD).
• MCD is much more likely to occur in people infected with HIV. Over the past few decades, as the number of people with HIV infection has increased, the number of people diagnosed with MCD has also gone up.
• Modern anti-viral treatments have helped people with HIV live much longer, but these drugs don’t seem to lower the chance of getting MCD.
• CD can affect children as well as adults. Younger people are more likely to have the localized form.
• Older adults and those with HIV infection are more likely to have the multicentric form.

For statistics related to survival, see Survival Rates for Castleman Disease.

We do not know exactly what causes Castleman disease (CD). The main feature of CD is an overgrowth of lymphocytes (immune cells) called B cells. The cause of this overgrowth is not known for sure, but it seems to be related to problems with the way a person’s immune system is working. Many people with CD have abnormally high blood levels of certain substances made by immune system cells.

For example, in the multicentric form of CD (MCD), the body often makes too much of a protein called interleukin-6 (IL-6). IL-6 normally helps regulate immune function. Too much IL-6 can cause lymphocytes to grow and divide too quickly. But it’s not clear what causes the high levels of IL-6.

One cause seems to be infection with human herpesvirus-8 (HHV-8), also known as Kaposi sarcoma herpesvirus (KSHV) (because it can cause Kaposi sarcoma). HHV-8 is often found in the lymph node cells in people who have MCD, especially those who are HIV positive. HHV-8 can cause infected cells to make a form of IL-6, which could explain how it leads to CD.

Many people are infected with HHV-8, but in people with normal immune systems the virus doesn’t seem to cause problems. People infected with HIV, however, often have weakened immune systems, which might allow HHV-8 to grow and cause problems. This could explain why people infected with HIV are more likely get MCD. Still, some people with HIV who develop MCD do not have weakened immune systems, so it’s not clear if this is the only reason.

HHV-8 hasn’t been found in all cases of MCD. And it’s not clear what causes the localized (unicentric) form of CD. Researchers are still looking for the causes of CD in these other cases.