About giant benign lymphoma
What is giant benign lymphoma?
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).
What are the symptoms for giant benign lymphoma?
UCD is characterized by a single enlarged lymph node or multiple enlarged lymph nodes in a single region of the body, such as the chest, abdomen, or neck. In most cases of UCD, individuals exhibit no symptoms (asymptomatic). Occasionally, patients experience symptoms due 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. Occasionally, individuals with UCD 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 typically seen in MCD. These symptoms usually disappear after surgical excision of the UCD lymph node.
Both HHV-8-associated MCD and iMCD are characterized by multiple regions of enlarged lymph nodes and episodic inflammatory symptoms, such as fever, weight loss, skin rash, 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). Many individuals with MCD may exhibit an abnormally large liver and spleen (hepatosplenomegaly).
HHV-8–associated MCD is most commonly diagnosed in HIV-infected or otherwise immunocompromised individuals. Thus, HHV-8-associated MCD patients may experience additional symptoms related to their HIV infection or other conditions.
What are the causes for giant benign lymphoma?
The exact cause of UCD and iMCD is not known. Viruses, genetic mutations acquired over the course of life, and inflammation have all been proposed as possible causes of UCD. Recent research suggests that acquired genetic mutations are the likely cause of UCD.
HHV-8 is the well-established cause of HHV-8-associated MCD, which accounts for approximately 50% of all cases of MCD. HHV-8-associated MCD often occurs in individuals infected with human immunodeficiency virus (HIV). The HIV weakens the immune system’s ability to control the HHV-8 infection. The HHV-8 virus causes MCD by making its own IL-6 and causing cells to proliferate.
Approximately 50% of MCD cases are negative for HHV-8 and the cause is unknown or “idiopathic.” Recently, four possible causes have been hypothesized: a virus, genetic mutation acquired over the course of life, an inherited genetic mutation, or autoimmunity. Some researchers speculate that increased production of interleukin-6 (IL-6) for one of the above causes may be involved in the development of iMCD. 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. However, IL-6 is not elevated in all cases, and neutralizing IL-6 is not effective for the treatment of all cases.
What are the treatments for giant benign lymphoma?
Treatment For localized (unicentric) disease, surgical removal of the affected lymph node(s) usually results in cure. However, recurrences of UCD have been reported. In some cases, ionizing radiation (radiotherapy) has proven effective.
For iMCD, chemotherapy had been the cornerstone of treatment, but has been largely supplanted by newer, more directed therapies. These include drugs which target and neutralize IL-6 (siltuximab or Sylvant) or the receptor for IL-6 (tocilizumab or Actemra). In 2014, Sylvant (siltuximab) was approved to treat patients with iMCD. This is the first and only FDA-approved drug to treat patients with iMCD. Approximately half of iMCD patients do not improve with IL-6 neutralization. These patients are often treated with chemotherapy or newer treatment options such as rituximab, sirolimus, or anakinra.
Additional symptomatic and supportive therapy may include corticosteroids or autologous bone marrow transplantation (used most frequently for severe disease or iMCD associated with POEMS syndrome).
For HHV-8-associated MCD, rituximab to eliminate a type of immune cell called the B lymphocyte is often used. It is highly effective for HHV-8-associated MCD, but occasionally antivirals and/or cytotoxic chemotherapies are needed.
What are the risk factors for giant benign lymphoma?
Castleman disease can affect people of any age. But the average age of people diagnosed with unicentric Castleman disease is 35. Most people with the multicentric form are in their 50s and 60s. The multicentric form is also slightly more common in men than in women.
The risk of developing multicentric Castleman disease is higher in people who are infected with a virus called human herpesvirus 8 (HHV-8).