Please refer to the below glossary for a listing of terms used throughout this site:
Autoimmune disease: a disease in which the immune system attacks normal healthy tissue, mistaking it for a foreign organism.
Autoinflammatory disease: a disease in which the immune system causes hyperinflammation due to genetic mutations that prevent it from being able to turn off inflammation.
B-cell: a type of lymphocyte whose primary function is to transform into plasma cells to produce antibodies that help neutralize foreign organisms; B cells also produce cytokines that regulate other immune system functions.
Benign: a term used to refer to tumor cells that are non-malignant. Lymph nodes of Castleman disease patients have been considered to be "benign" for many years, but this is a misnomer because the lymph nodes of Castleman disease patients are not tumors. The cells within the lymph node are proliferating due to high levels of inflammatory proteins (chemokines and cytokines), not because they are benign tumors or because there are malignant cells.
Chemokines and Cytokines: chemical substances that immune cells use to communicate with other immune cells. For instance, immune cells may release a cytokine called interleukin-1 (IL-1) to alert the other cells of the immune system that they may need to fight off an invading bacteria or virus. In CD, these proteins in the blood are thought to contribute to CD symptoms.
Diagnostic Criteria: in January 2017, the CDCN published the first-ever diagnostic criteria for HHV-8-negative/idiopathic (iMCD) that defines what physicians shoudl look out for and what they need to rule out to diagnose CD. An international group of 34 expert physicians from eight countries on five continents created these diagnostic criteria, then published in the top hematology journal, Blood. Click here.
Doctors/Specialists: a primary care physician (PCP) may treat CD or may prefer to make a referral to a specialist, which may include a surgeon, a medical oncologist, a hematologist-oncologist, a virologist, or a radiation/oncologist.
Human herpesvirus-8 (HHV-8): also known as Kaposi’s sarcoma-associated herpesvirus, HHV-8 is one of seven currently known cancer-causing viruses (oncoviruses). Because most healthy immune systems are able to prevent the spread of this virus, HHV-8 usually only causes problems in individuals with immunosuppressed or weakened immune systems (e.g., HIV infected). In HHV-8-associated MCD, HHV-8 signals for the release of cytokines by the body that result in MCD. HHV-8 lives in the body’s B-cells, so destruction of these B-cells with Rituxan (rituximab) is a very effective treatment strategy in HHV-8-associated MCD.
HHV-8-associated MCD (Human Herpesvirus-8-associated MCD): this is a group of MCD patients whose lymph nodes test positive for HHV-8, thought to comprise 50%. No medications are approved specifically for treatment of HHV-8-associated MCD, though patients tend to respond well to rituximab.
HHV-8-negative MCD (Human Herpesvirus-8-negatiev MCD): also known as idiopathic MCD. This is a group of MCD patients whose lymph nodes test negatiev for HHV-8, thought to comprise 50%. Siltuximab (Sylvant) is the only treatment approved by the FDA specifically for this patient population, which means the drug has been studied in ths patient population and proven to be effective in some patients.
Hypercytokinemia: a state of elevated levels of cytokines in the blood.
Hyperinflammatory disorder: a disorder involving the excessive activation of immune cells and subsequent release of inflammatory chemical messengers (chemokines and cytokines). There are a variety of triggers for the immune cell activation such as foreign organisms, autoimmune mechanisms, and organ transplant rejection.
Idiopathic: the term often given to diseases for which the cause is unknown.
Idiopathic MCD (iMCD): also known as HHV-8-negative MCD, the origin of this subtype of CD is unknown.
Immune system: a healthy immune system involves a complex network of cells and proteins that fight infections throughout the body. Lymph nodes are the home base for immune cells.
Interleukin-6 (IL-6): one type of cytokine, which is found and used by every healthy immune system. It is often found to be abnormally elevated in Castleman disease as a source of hyperinflammation and is thus a therapeutic target. This is what siltuximab and tocilizumab block.
Lymph node: one of many small organs that are distributed throughout the body with the function of filtering the blood for foreign particles and serving as the location that activated immune cells go to to work together. Lymph nodes get enlarged during states of inflammation. This is where many lymphocytes, including B-cells, T-cells, and plasma cells are concentrated.
Lymphocyte: a type of white blood cell (immune cell) used to fight infections but can occasionally drive diseases by attacking normal tissue directly or releasing cytokines. Includes B-cells, T-cells, and plasma cells. The lymph node is the home base for these cell types.
Lymphoproliferative disorder: a disorder involving the abnormally rapid production (proliferation) of lymphocytes. This typically refers to diseases where the proliferation is due to a malignant mutation, such a lymphoma or multiple myeloma. Castleman disease is often considered to be a lymphoproliferative disorder because lymphocytes proliferate due to cytokine signaling, but researchers are beginning to think it should be more appropriately considered as a hyperinflammatory disorder.
Multicentric Castleman disease (MCD): comprises approximately 30% of CD patients. It involves more than one region of enlarged lymph nodes. MCD symptoms can range from no symptoms to severe symptoms requiring hospitalization, including fatigue, night sweats, fevers, weight loss, and organ dysfunction. Most patients are diagnosed in their mid-50's, but again the range can be from small children to senior citizens. There is no known cure for MCD, but symptoms may be managed with medications.
MCD can also be broken down into histological subtypes (such as hyaline vascular, plasma cell, mixed cell, or plasmablastic), which is helpful to continue to learn more about the disease and how it works.
Neoplastic: a term used to refer to tumor cells that are malignant or cancerous.
Paraneoplastic syndrome: a disease in which cancerous cells release substances or cause the release of substances that generate a separate set of symptoms in the patient not directly associated with the malignancy.
Pathologist: a doctor that interprets changes caused by diseases in tissues and body fluids. Hematopathologist is a pathologist that specializes in diseases of the blood and lymphoid tissues, such as CD.
Plasma cell: a type of lymphocyte that produces large quantities of antibodies, which are proteins used by the immune system to destroy bacteria and viruses; B-cells become plasma cells during their final stage of maturation.
T-cell: a type of lymphocyte involved in killing other cells infected with organisms.
TAFRO syndrome: stands for thrombocytopenia, anasarca, fever, reticulin fibrosis, organomegaly. It is a variant of HHV-8-negative MCD recently described in Japan.
Tests: there is no single test that can diagnose CD. Some examples of tests that are required to make a diagnosis of CD include: physical examination, blood tests, imaging tests such as X-rays, MRI, CT, or PET scans, and lymph node biopsies.
Unicentric Castleman disease (UCD): comprises approximately 70% of CD patients. It involves a single lymph node or one region of enlarged lymph nodes. UCD patients tend to have limited symptoms but may be uncomfortable wiht the feeling of an enlarged lymph node. Most patients are diagnosed in their mid-30's, but it can affect people at any age. Typically, UCD is treated with surgical removal of enlarged lymph nodes. Many people are cured with surgery if complete removal of swollen lymph nodes is achieved. Sometimes swollen lymph nodes cannot be removed and these patients may continue to have symptoms.
After UCD patients successfully have their lymph nodes removed, they may have a UCD recurrence. UCD recurrence is considered enlargement of lymph node(s) in a single region of the body after complete removal of initial swollen lymph nodes. These recurrences may occur in the same location as the first lymph node(s) enlargement or it may occur in a different region of the body.