Castleman's disease is a rare disorder characterized by non-cancerous (benign) growths (tumors) that may develop in the lymph node tissue throughout the body (i.e., systemic disease). Most often, they occur in the chest, abdomen, and/or neck, but may also be found in the armpit (axilla), pelvis, and pancreas. Usually the growths represent abnormal enlargement of the lymph nodes normally found in these areas.
Castleman's disease may be divided into four types. There are two main types of Castleman's disease that are determined by the microscopic appearance of the lymph node: hyaline-vascular type and plasma cell type. The hyaline vascular type accounts for approximately 90 percent of the cases. Most individuals exhibit no symptoms of this form of the disorder (asymptomatic) or they may develop non-cancerous growths in the lymph nodes. The plasma cell type of Castleman's disease may be associated with fever, weight loss, skin rash, early destruction of red blood cells, leading to unusually low levels of circulating red blood cells (hemolytic anemia), and/or abnormally increased amounts of certain immune factors in the blood (hypergammaglobulinemia). Additionally, Castleman's disease can be divided into categories which are defined by number of anatomic body regions affected by the disease. Unicentric Castleman's disease affects lymph nodes in only one part of the body, while multicentric Castleman's disease affects multiple parts of the body. A person can have any combination of the microscopic and anatomic variants, thus there are four possibilities: unicentric hyaline vascular, unicentric plasma cell variant, multicentric hyaline vascular variant, and multicentric plasma cell variant. Many individuals with multicentric Castleman's disease may exhibit an abnormally large liver and spleen (hepatosplenomegaly).
In most cases, Castleman’s disease is characterized by a single, solid growth within lymphatic tissue in the chest, stomach, or neck. Growths may also occur in other lymphatic tissue throughout the body. Usually the growths represent abnormal enlargement of the lymph nodes normally found in these areas.
In most cases of the unicentric hyaline-vascular variant of Castleman’s disease, individuals exhibit no symptoms (asymptomatic) or may develop a non-cancerous (benign) growth in the lymph tissue; most frequently in the chest. Symptoms with this type are usually secondary to the size and location of the growth. For example, a growth may form next to a vein, resulting in a bulge and possible obstruction in the involved blood vessel.
In the plasma cell variants of Castleman’s disease, individuals may exhibit a variety of symptoms including fever, fatigue, excessive sweating, weight loss, skin rash, early destruction of red blood cells, leading to unusually low levels of circulating red blood cells (hemolytic anemia), and/or abnormally elevated amounts of certain immune factors in the blood (hypergammaglobulinemia). These symptoms are also occasionally seen with the multicentric hyaline vascular variant.
Some cases of multicentric Castleman’s disease have been associated with POEMS syndrome. (For more information on this disorder, choose “POEMS” as your search term in the Rare Disease Database.) Researchers have speculated that individuals with this type of Castleman’s disease may have a greater risk of developing malignant complications such as Kaposi’s sarcoma or malignant lymphoma.
The exact cause of Castleman’s disease is not known. Some researchers speculate that increased production of interleukin-6 (IL-6) may be involved in the development of Castleman’s disease. IL-6 is a substance normally produced by cells within the lymph nodes (plasma cells) and in healthy individuals serves to coordinate the immune response to infection. Recently, a virus has been found to be the cause of some cases of multicentric Castleman’s disease. Human herpesvirus 8 (also known as HHV-8, Kaposi’s sarcoma-associated herpesvirus, or KSHV) is found in nearly all patients with human immunodeficiency virus (HIV) who develop multicentric Castleman’s disease and up to 60% of patients without HIV. The virus may cause Castleman’s disease by making its own IL-6. In persons who are not infected with HHV-8, it is thought that the excess IL-6 may be caused by a genetic mutation in a gene known as the interleukin 6 promoter.
Castleman’s disease is a rare disorder of the lymphatic system that affects males and females in equal numbers. All types of Castleman’s disease may affect individuals of any age; however, the plasma cell type has greater prevalence among young males and females. Children are rarely affected by this disorder. Persons with HIV are at increased risk of developing multicentric Castleman’s disease. It is estimated that there are approximately 30,000 individuals in the United States afflicted with Castleman’s disease.
The diagnosis of Castleman's disease may be based upon a thorough clinical evaluation that includes a detailed patient history and a variety of specialized imaging techniques (e.g., computer-assisted tomography [CT scan], magnetic resonance imaging [MRI], and ultrasonography). During CT scanning, a computer and X-rays are used to create a film showing cross-sectional images of an organ's tissue structure. MRI uses a magnetic field and radio waves to create cross-sectional images of the organ. In ultrasonography, reflected sound waves create an image of the organs in question. These tests can identify abnormal growths associated with Castleman's disease. Identifying the presence of elevated levels of interleukin-6 may also assist a diagnosis of Castleman's disease, as can the detection of human herpesvirus-8 among patients with the mullticentric variant. A definitive diagnosis of Castleman's disease can not be made in the absence of a surgical (excisional) biopsy of the lymph node.
The treatment of Castleman's Disease is directed toward the specific symptoms that are apparent in each individual. For localized (unicentric) disease, surgical removal of the affected lymph node(s) usually results in cure. In some cases, ionizing radiation (radiotherapy) has proven effective. For multicentric disease, chemotherapy and radiation had been the cornerstones of treatment, but have been largely supplanted by newer, more directed therapies. These include a drug which targets the IL-6-producing plasma cells for destruction (rituximab) and drugs which either block the action of IL-6 (tocilizumab or Actemra) or scavenge IL-6 from the bloodstream (siltuximab or CNTO328) . Additional symptomatic and supportive therapy may include corticosteroids or autologous bone marrow transplantation (used most frequently for severe disease or disease associated with POEMS syndrome).
As of 2010, an ongoing clinical research study is enrolling patients with Castleman’s disease. The purpose of this Phase II study is to evaluate the efficacy of a drug known as siltuximab(CNTO 328),, an anti-IL-6 antibody. . Results of the Phase I study indicated that nearly 80% of patients responded to treatment with minimal side effects. This study is being conducted at more than 70 centers across the world. For more information, go to www.castlemansresearch.com.
The drug, tocilizumab (Actemra), manufactured by Roche Pharmaceuticals in the United States, showed substantial efficacy in the treatment of Castleman’s in a small study from Japan. The drug has been approved by the US Food and Drug Administration for the treatment of Rheumatoid arthritis, and can be prescribed “off label” for the treatment of Castleman’s. Treatment requires monthly intravenous injections.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.
For information about clinical trials being conducted by the National Institutes of Health (NIH) Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
For information about clinical trials sponsored by private sources, contact:
Contact for additional information about Castleman’s disease:
Corey Casper, MD MPH
Associate Professor of Medicine, University of Washington
Assistant Member, Fred Hutchinson Cancer Research Center
Medical Director of Infection Control, Seattle Cancer Care Alliance
1100 Fairview Ave. North
Seattle, Washington 98109
Phone: (206) 667-4600, Fax: (206) 667-1965
Office Location: M1-B849
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