Castleman's disease
Encyclopedia
Castleman's disease is an uncommon lymphoproliferative disorder that can involve single lymph node stations or
can be systemic. It must be distinguished from reactive lymph node hyperplasia
and malignancies. It is a very rare disorder characterized by non-cancerous growths (tumors) that may develop in the lymph node tissue at a single site or throughout the body. It involves hyperproliferation of certain B cell
s that often produce cytokine
s. While not officially considered a cancer, the overgrowth of lymphocytes with this disease is similar to lymphoma.
It is named for Benjamin Castleman
.
In most of the cases, Castleman's disease is likely due to hypersecretion of the cytokine IL-6
, but some patients may have normal IL-6 levels and present with non-iron-deficient microcytic anemia.
Multicentric Castleman's disease (MCD) involves growths at multiple sites. About 50% is caused by KSHV, also called HHV-8, a gammaherpesvirus that is also the cause of Kaposi's sarcoma
and primary effusion lymphoma
, while the remainder of MCD are of unknown cause. The form of MCD most closely associated with KSHV is the plasmacytic form of Castleman's disease while another pathologic form, the hyaline-vascular form, is generally negative for this virus.
. Symptomatically, therefore, MCD can be difficult to diagnose and even in the case of a lymph-node biopsy a conclusive diagnosis remains problematic.
Castleman's is seen in POEMS syndrome
and is implicated in 10% of cases of paraneoplastic pemphigus
.
is often curative, and the prognosis is excellent.
It is important to distinguish AIDS-related Multicentric Castleman’s disease from other forms of Multicentric Castleman’s disease. Treatment for the former can be focused upon the same protocols used for treating the underlying AIDS.
Prior to 1996 MCD carried a poor prognosis of about 2 years, due to autoimmune hemolytic anemia
and non-Hodgkin's lymphoma which may arise as a result of proliferation of infected cells. The timing of diagnosis, with particular attention to the difficulty of determining the cause of B symptoms without a CT scan and lymph node biopsy, may impact significantly on the prognosis and risk of death. Left untreated, MCD usually gets worse and becomes increasingly difficult and unresponsive to current treatment regimens.
Recent work with HIV-positive patients with KSHV-related MCD suggests that treatment with the antiherpesvirus drug ganciclovir
or the antiCD20 B cell monoclonal antibody, rituximab
, may markedly improve outcome. These drugs target and kill B cells via the B cell specific CD20 marker. Since B cells are required for the production of antibodies, the body's immune response is weakened whilst on treatment and the risk of further viral or bacterial infection is increased. Due to the uncommon nature of the condition there are not many large scale research studies from which standardized approaches to therapy may be drawn, and the extant case studies of individuals or small cohorts should be read with caution. As with many diseases, the patient's age, physical state and previous medical history with respect to infections may impact on the disease progression and outcome.
Use of tocilizumab
has been proposed.
Other treatments for multicentric castleman disease include the following:
can be systemic. It must be distinguished from reactive lymph node hyperplasia
and malignancies. It is a very rare disorder characterized by non-cancerous growths (tumors) that may develop in the lymph node tissue at a single site or throughout the body. It involves hyperproliferation of certain B cell
B cell
B cells are lymphocytes that play a large role in the humoral immune response . The principal functions of B cells are to make antibodies against antigens, perform the role of antigen-presenting cells and eventually develop into memory B cells after activation by antigen interaction...
s that often produce cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
s. While not officially considered a cancer, the overgrowth of lymphocytes with this disease is similar to lymphoma.
It is named for Benjamin Castleman
Benjamin Castleman
Benjamin Castleman was an American pathologist best known for the eponymous disease which is named after him, Castleman's disease....
.
Types
There are several variants of Castleman's disease.In most of the cases, Castleman's disease is likely due to hypersecretion of the cytokine IL-6
Interleukin 6
Interleukin-6 is a protein that in humans is encoded by the IL6 gene.IL-6 is an interleukin that acts as both a pro-inflammatory and anti-inflammatory cytokine. It is secreted by T cells and macrophages to stimulate immune response, e.g. during infection and after trauma, especially burns or other...
, but some patients may have normal IL-6 levels and present with non-iron-deficient microcytic anemia.
- In tumors that are positive for Kaposi's sarcoma-associated herpesvirusKaposi's sarcoma-associated herpesvirusKaposi's sarcoma-associated herpesvirus is one of seven currently known human cancer viruses, or oncoviruses. It is also the eighth human herpesvirus; its formal name according to the International Committee on Taxonomy of Viruses is HHV-8. Like other herpesviruses, its informal name is used...
(KSHV), also called human herpes virus 8 (HHV-8), this is most likely due to expression of the virus-encoded cytokine, vIL-6. - KSHV negative tumors appear to be the result of over-secretion of human IL-6.
Unicentric vs. multicentric
Unicentric Castleman's disease involves tissue growths at only a single site. It usually has few or no symptoms other than those directly associated with the physical enlargement of the lymph node. In 90% or more, removal of the enlarged node is curative, with no further complications. However, in 2011, Weng et al. described a patient with unicentric Castleman's disease, hyaline vascular type, presenting with severe chronic non-iron-deficient anemia. He suggested that in patients with normal IL-6 level may present with non-iron deficient type and may resolve after effective treatment of Castleman's disease.Multicentric Castleman's disease (MCD) involves growths at multiple sites. About 50% is caused by KSHV, also called HHV-8, a gammaherpesvirus that is also the cause of Kaposi's sarcoma
Kaposi's sarcoma
Kaposi's sarcoma is a tumor caused by Human herpesvirus 8 , also known as Kaposi's sarcoma-associated herpesvirus . It was originally described by Moritz Kaposi , a Hungarian dermatologist practicing at the University of Vienna in 1872. It became more widely known as one of the AIDS defining...
and primary effusion lymphoma
Primary effusion lymphoma
-Causes:It is caused by Kaposi's sarcoma-associated herpesvirus , also known as human herpesvirus 8 .In most cases, the lymphoma cells are also infected with Epstein Barr virus ....
, while the remainder of MCD are of unknown cause. The form of MCD most closely associated with KSHV is the plasmacytic form of Castleman's disease while another pathologic form, the hyaline-vascular form, is generally negative for this virus.
MCD Symptoms
The most common 'B Symptoms' of MCD are high fevers, anemia, weight loss, loss of appetite, and low white blood cell counts, which may to be due to the overproduction of interleukin 6Interleukin 6
Interleukin-6 is a protein that in humans is encoded by the IL6 gene.IL-6 is an interleukin that acts as both a pro-inflammatory and anti-inflammatory cytokine. It is secreted by T cells and macrophages to stimulate immune response, e.g. during infection and after trauma, especially burns or other...
. Symptomatically, therefore, MCD can be difficult to diagnose and even in the case of a lymph-node biopsy a conclusive diagnosis remains problematic.
Castleman's is seen in POEMS syndrome
POEMS syndrome
POEMS syndrome is a rare medical syndrome. It is defined as the combination of a plasma-cell proliferative disorder , polyneuropathy, and effects on many other organ systems. It begins in middle age – the average age at onset is 50 – and affects up to twice as many men as women...
and is implicated in 10% of cases of paraneoplastic pemphigus
Paraneoplastic pemphigus
Paraneoplastic pemphigus is an autoimmune disorder that is almost invariably linked to an underlying lymphoproliferative disorder.-External links:*Wikipedia Pemphigus Page with PNP Information*...
.
Unicentric
In the Unicentric form of the disease, surgical resectionSegmental resection
Segmental resection is a surgical procedure to remove part of an organ or gland. It may also be used to remove a tumor and normal tissue around it. In lung cancer surgery, segmental resection refers to removing a section of a lobe of the lung.- External links :* entry in the public domain NCI...
is often curative, and the prognosis is excellent.
Multicentric
There is no standard therapy for MCD at the moment.It is important to distinguish AIDS-related Multicentric Castleman’s disease from other forms of Multicentric Castleman’s disease. Treatment for the former can be focused upon the same protocols used for treating the underlying AIDS.
Prior to 1996 MCD carried a poor prognosis of about 2 years, due to autoimmune hemolytic anemia
Autoimmune hemolytic anemia
Autoimmune hemolytic anemia occurs when antibodies directed against the person's own red blood cells cause the RBCs to burst , leading to insufficient plasma concentration. The lifetime of the RBCs is reduced from the normal 100–120 days to just a few days in serious cases...
and non-Hodgkin's lymphoma which may arise as a result of proliferation of infected cells. The timing of diagnosis, with particular attention to the difficulty of determining the cause of B symptoms without a CT scan and lymph node biopsy, may impact significantly on the prognosis and risk of death. Left untreated, MCD usually gets worse and becomes increasingly difficult and unresponsive to current treatment regimens.
Recent work with HIV-positive patients with KSHV-related MCD suggests that treatment with the antiherpesvirus drug ganciclovir
Ganciclovir
Ganciclovir INN is an antiviral medication used to treat or prevent cytomegalovirus infections.Ganciclovir sodium is marketed under the trade names Cytovene and Cymevene . Ganciclovir for ocular use is marketed under the trade name Vitrasert...
or the antiCD20 B cell monoclonal antibody, rituximab
Rituximab
Rituximab, sold under the trade names Rituxan and MabThera, is a chimeric monoclonal antibody against the protein CD20, which is primarily found on the surface of B cells...
, may markedly improve outcome. These drugs target and kill B cells via the B cell specific CD20 marker. Since B cells are required for the production of antibodies, the body's immune response is weakened whilst on treatment and the risk of further viral or bacterial infection is increased. Due to the uncommon nature of the condition there are not many large scale research studies from which standardized approaches to therapy may be drawn, and the extant case studies of individuals or small cohorts should be read with caution. As with many diseases, the patient's age, physical state and previous medical history with respect to infections may impact on the disease progression and outcome.
Use of tocilizumab
Tocilizumab
Tocilizumab is an immunosuppressive drug, mainly for the treatment of rheumatoid arthritis and systemic juvenile idiopathic arthritis, a severe form of RA in children. It is a humanized monoclonal antibody against the interleukin-6 receptor...
has been proposed.
Other treatments for multicentric castleman disease include the following:
- Corticosteroids
- ChemotherapyChemotherapyChemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
- ThalidomideThalidomideThalidomide was introduced as a sedative drug in the late 1950s that was typically used to cure morning sickness. In 1961, it was withdrawn due to teratogenicity and neuropathy. There is now a growing clinical interest in thalidomide, and it is introduced as an immunomodulatory agent used...