Materiały źródłowe

• #1 Castleman Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK576394/

  Castleman disease is a lymphoproliferative disorder with a nondefinite etiology and can be classified into subtypes based on clinical and histological manifestations. […] There is very little knowledge available about the etiology of this disorder, but some evidence that has been collected claims it to be a result of impaired immunoregulation that causes abundant proliferation of B lymphocytes and plasma cells in lymphoid organs. These conditions can result from chronic low-grade inflammation, lymphoid-hamartomatous hyperplasia, viral infections, abnormal modulation of cytokines, and angiogenesis. […] In addition, a very close association of the disease with HIV has been discovered, which puts immunodeficiency on the list as well. Particularly in MCD, the causative factors include human herpesvirus (HHV)-8, which causes deregulation of the inflammatory mediators like CD20 and interleukin (IL)-6. […] Almost all cases of HIV-associated Castleman disease are HHV-8 positive, compared to 40 to 50% of non-HIV CD. The remaining cases unrelated to HIV or HHV-8, termed idiopathic multicentric CD (iMCD), have no established etiology to date.

• #2 Castleman Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/sites/books/NBK576394/?report=reader

  Castleman disease is a lymphoproliferative disorder with a nondefinite etiology and can be classified into subtypes based on clinical and histological manifestations. […] There is very little knowledge available about the etiology of this disorder, but some evidence that has been collected claims it to be a result of impaired immunoregulation that causes abundant proliferation of B lymphocytes and plasma cells in lymphoid organs. […] In addition, a very close association of the disease with HIV has been discovered, which puts immunodeficiency on the list as well. […] Particularly in MCD, the causative factors include human herpesvirus (HHV)-8, which causes deregulation of the inflammatory mediators like CD20 and interleukin (IL)-6. […] Almost all cases of HIV-associated Castleman disease are HHV-8 positive, compared to 40 to 50% of non-HIV CD. The remaining cases unrelated to HIV or HHV-8, termed idiopathic multicentric CD (iMCD), have no established etiology to date.

• #3 Overview – Castleman Disease Collaborative Network | CDCN

  https://cdcn.org/castleman-disease/overview/

  Castleman disease (CD) describes a group of rare disorders that involve enlarged lymph nodes with a similar lymph node appearance under the microscope and a broad range of inflammatory symptoms and laboratory abnormalities. […] Whether Castleman disease should be considered an autoimmune disease, cancer, or infectious disease is currently unknown. […] MCD is further sub-classified based on the underlying cause: POEMS-associated MCD, HHV-8-associated multicentric Castleman disease and idiopathic multicentric Castleman disease (iMCD). […] POEMS-associated MCD involves a cancerous cell population found in patients with POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes) that can cause excessive cytokine production and MCD in a fraction of patients.

• #4 Castleman Disease | Condition | UAMS Health

  https://uamshealth.com/condition/castleman-disease/

  Castleman Disease (CD) describes a group of rare lymphoproliferative disorders that involve enlarged lymph nodes with characteristic microscopic changes and a broad range of inflammatory symptoms and laboratory abnormalities. […] Whether Castleman disease should be considered an autoimmune disease, cancer, or infectious disease is currently unknown. […] Multicentric CD (MCD) can be caused by a cancerous cell population (referred to as POEMS-associated MCD), an infection with human herpesvirus-8 (HHV-8-associated MCD), or an unknown cause (idiopathic MCD) where there are signs of autoimmunity but no evidence of an infection or a cancer. […] Thus, the various subtypes of CD can be described as either a benign tumor, a cancerous syndrome, an infectious disorder, or an autoimmune disease.

• #5 Castleman Disease: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/2219018-overview

  The etiologies differ between the four subtypes of Castleman disease. […] The etiology of UCD is unknown, but a subset of UCD cases may be the result of somatic mutations in monoclonal cell populations, likely lymph node stromal cells. Alternatively, UCD may occur due to exaggerations of the types of reactive changes that can be seen in response to normal antigenic stimuli. […] Active HHV-8 infection is the well-established etiology of HHV-8associated MCD. HHV-8 is a gamma herpesvirus similar to Epstein-Barr virus (EBV) that has been found in both endemic and HIV-associated Kaposi sarcoma (KS). The HHV-8 virus is pathologically responsible for all symptoms and signs of the disease. […] The etiology of HHV-8negative/idiopathic MCD (iMCD) is not known. The heterogeneity of clinical features and pathologic abnormalities, which overlap with a wide range of other immunologic disorders, suggests that multiple processes each involving immune dysregulation and a common pathway of increased cytokine levels may give rise to iMCD in different subsets of patients. Four candidate etiologic drivers of iMCD pathogenesis have been proposed: autoimmune, autoinflammatory, neoplastic, and/or infectious mechanisms.

• #6

• #7 Castleman Disease: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/2219018-overview

  The etiologies differ between the four subtypes of Castleman disease. […] The etiology of UCD is unknown, but a subset of UCD cases may be the result of somatic mutations in monoclonal cell populations, likely lymph node stromal cells. Alternatively, UCD may occur due to exaggerations of the types of reactive changes that can be seen in response to normal antigenic stimuli. […] Active HHV-8 infection is the well-established etiology of HHV-8associated MCD. HHV-8 is a gamma herpesvirus similar to Epstein-Barr virus (EBV) that has been found in both endemic and HIV-associated Kaposi sarcoma (KS). The HHV-8 virus is pathologically responsible for all symptoms and signs of the disease. […] The etiology of HHV-8negative/idiopathic MCD (iMCD) is not known. The heterogeneity of clinical features and pathologic abnormalities, which overlap with a wide range of other immunologic disorders, suggests that multiple processes each involving immune dysregulation and a common pathway of increased cytokine levels may give rise to iMCD in different subsets of patients. Four candidate etiologic drivers of iMCD pathogenesis have been proposed: autoimmune, autoinflammatory, neoplastic, and/or infectious mechanisms.

• #8 About Castleman Disease – Castleman Disease Collaborative Network

  https://cdcn.org/castleman-disease/

  Castleman disease (CD) is a group of three immune system disorders that share a similar lymph node appearance under the microscope, but have different symptoms, causes, and treatments. […] All cases of unicentric Castleman disease (UCD) and HHV-8-negative multicentric Castleman disease (iMCD) are idiopathic, which means that the cause is not known. There are also no known risk factors for UCD or iMCD, though the possibility of a genetic cause is being researched. In HHV-8-associated multicentric Castleman disease, the HHV-8 virus causes and drives the disease.

• #9 Castleman Disease: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/2219018-overview

  The etiologies differ between the four subtypes of Castleman disease. […] The etiology of UCD is unknown, but a subset of UCD cases may be the result of somatic mutations in monoclonal cell populations, likely lymph node stromal cells. Alternatively, UCD may occur due to exaggerations of the types of reactive changes that can be seen in response to normal antigenic stimuli. […] Active HHV-8 infection is the well-established etiology of HHV-8associated MCD. HHV-8 is a gamma herpesvirus similar to Epstein-Barr virus (EBV) that has been found in both endemic and HIV-associated Kaposi sarcoma (KS). The HHV-8 virus is pathologically responsible for all symptoms and signs of the disease. […] The etiology of HHV-8negative/idiopathic MCD (iMCD) is not known. The heterogeneity of clinical features and pathologic abnormalities, which overlap with a wide range of other immunologic disorders, suggests that multiple processes each involving immune dysregulation and a common pathway of increased cytokine levels may give rise to iMCD in different subsets of patients. Four candidate etiologic drivers of iMCD pathogenesis have been proposed: autoimmune, autoinflammatory, neoplastic, and/or infectious mechanisms.

• #10 Castleman Disease: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/2219018-overview

  The etiologies differ between the four subtypes of Castleman disease. […] The etiology of UCD is unknown, but a subset of UCD cases may be the result of somatic mutations in monoclonal cell populations, likely lymph node stromal cells. Alternatively, UCD may occur due to exaggerations of the types of reactive changes that can be seen in response to normal antigenic stimuli. […] Active HHV-8 infection is the well-established etiology of HHV-8associated MCD. HHV-8 is a gamma herpesvirus similar to Epstein-Barr virus (EBV) that has been found in both endemic and HIV-associated Kaposi sarcoma (KS). The HHV-8 virus is pathologically responsible for all symptoms and signs of the disease. […] The etiology of HHV-8negative/idiopathic MCD (iMCD) is not known. The heterogeneity of clinical features and pathologic abnormalities, which overlap with a wide range of other immunologic disorders, suggests that multiple processes each involving immune dysregulation and a common pathway of increased cytokine levels may give rise to iMCD in different subsets of patients. Four candidate etiologic drivers of iMCD pathogenesis have been proposed: autoimmune, autoinflammatory, neoplastic, and/or infectious mechanisms.

• #11 Castleman Disease : Introduction

  https://www.webpathology.com/images/hematopathology/lymph-node-non-hematopoietic/lymphadenopathies—i/38565

  Castleman disease is a rare disorder involving lymph nodes and related tissues. Localized variant is of unknown etiology and presents as a mass-like enlargement of mediastinal or cervical lymph nodes without additional symptoms. […] However, evidence of monoclonality in lymph node stromal cells in recent studies have led to the suggestion that is may be a neoplasm. Multicentric Castleman disease has been linked to infection with human herpesvirus 8 (HHV8) in both HIV+ and HIV- individuals.

• #12

  https://haematologica.org/article/view/haematol.2021.280370

  Castleman disease is a polyclonal lymphoproliferative disorder characterized by unicentric or multicentric lymphadenopathy with characteristic histomorphological features, in addition to variable inflammatory symptomatology. […] The molecular mechanisms and etiologies of unicentric Castleman disease (UCD) and idiopathic multicentric Castleman disease (iMCD) are poorly understood, and identification of targetable disease mediators remains an unmet clinical need. […] The cellular and molecular mechanisms of UCD and iMCD are poorly understood. Most evidence points to an inflammatory process mediated by interleukin (IL)-6, vascular endothelial growth factor (VEGF) and/or chemokines in iMCD, compared to a lymphoproliferative process likely mediated by dysregulated lymph node stromal cells in UCD. However, the etiology of these processes is completely unknown.

• #13 Understanding Unicentric and Multicentric Castleman Disease

  https://www.healthline.com/health/castlemans-disease

  Some people with Castleman disease have no symptoms at all, while other people have symptoms that are similar to the flu. The exact cause of Castleman disease isnt known, but having HIV is the largest risk factor for developing the condition. […] The exact cause of Castleman disease is unknown. Its likely that the different types of Castleman disease have different underlying causes. […] Researchers believe that UCD is caused by a genetic mutation, and they are studying multiple different possibilities. A mutation called PDGFRB has been documented in multiple cases of UCD and idiopathic MCD. […] Having HIV is a major risk factor in developing MCD. This is due in part to people with HIV having an increased chance of getting a specific virus associated with Castleman. […] Almost all cases of MCD are linked to an infection with human herpesvirus type 8 (HHV-8), which can cause the cancer Kaposi sarcoma. […] When the disease is not linked to HHV-8, it is called idiopathic multicentric Castleman disease, meaning the cause is unknown. […] UCD is more common and seems to result from a genetic mutation. MCD almost always results from contracting the HHV-8 virus, and having HIV is a major risk factor.

• #14 Castleman disease | City of Hope

  https://www.cancercenter.com/risk-factors/castleman-disease

  Castleman disease (CD) is a rare condition that affects the lymph nodes and related tissues. […] The exact cause of Castleman disease isnt known, and there are no known risk factors. Factors such as viruses, genetic mutations acquired over the course of life, an inherited genetic mutation, autoimmunity and inflammation may contribute to the disease. […] Recent research suggests that acquired genetic mutations seem to be the main cause of UCD, and some scientists theorize that an increased production of IL-6 by the immune system may contribute to the disease by causing an overgrowth of lymphatic cells, leading to many of the flu-like signs and other symptoms of CD. […] The HHV-8 present in many patients with MCD is also found in nearly all people who are HIV-positive. HIV weakens the immune systems ability to control the HHV-8 infection, and its thought that HHV-8 then causes MCD by making its own IL-6 and an overabundance of lymphatic cells.

• #15 Overview – Castleman Disease Collaborative Network | CDCN

  https://cdcn.org/castleman-disease/overview/

  Castleman disease (CD) describes a group of rare disorders that involve enlarged lymph nodes with a similar lymph node appearance under the microscope and a broad range of inflammatory symptoms and laboratory abnormalities. […] Whether Castleman disease should be considered an autoimmune disease, cancer, or infectious disease is currently unknown. […] MCD is further sub-classified based on the underlying cause: POEMS-associated MCD, HHV-8-associated multicentric Castleman disease and idiopathic multicentric Castleman disease (iMCD). […] POEMS-associated MCD involves a cancerous cell population found in patients with POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes) that can cause excessive cytokine production and MCD in a fraction of patients.

• #16 Castleman Disease | Children’s Hospital of Philadelphia

  https://www.chop.edu/conditions-diseases/castleman-disease

  Castleman disease is a rare immune dysregulation disorder where an overgrowth of cells in your childs lymph nodes causes them to be enlarged and sometimes also causes fevers or other signs of systemic inflammation (when the immune system is constantly defending the body). […] We do know that children with viruses like human herpes virus type 8 (HHV-8) or human immunodeficiency virus (HIV) can also become affected by Castleman disease. […] The second type of MCD is associated with a virus called human herpes virus type 8 (HHV-8). It can sometimes also be associated with human immunodeficiency virus, or HIV. This is called HHV-8-associated MCD. […] The third type of MCD has no known cause, but it is not due to infection from HHV-8. This is called idiopathic MCD (iMCD).

• #17 Castleman Disease: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/2219018-overview

  The etiologies differ between the four subtypes of Castleman disease. […] The etiology of UCD is unknown, but a subset of UCD cases may be the result of somatic mutations in monoclonal cell populations, likely lymph node stromal cells. Alternatively, UCD may occur due to exaggerations of the types of reactive changes that can be seen in response to normal antigenic stimuli. […] Active HHV-8 infection is the well-established etiology of HHV-8associated MCD. HHV-8 is a gamma herpesvirus similar to Epstein-Barr virus (EBV) that has been found in both endemic and HIV-associated Kaposi sarcoma (KS). The HHV-8 virus is pathologically responsible for all symptoms and signs of the disease. […] The etiology of HHV-8negative/idiopathic MCD (iMCD) is not known. The heterogeneity of clinical features and pathologic abnormalities, which overlap with a wide range of other immunologic disorders, suggests that multiple processes each involving immune dysregulation and a common pathway of increased cytokine levels may give rise to iMCD in different subsets of patients. Four candidate etiologic drivers of iMCD pathogenesis have been proposed: autoimmune, autoinflammatory, neoplastic, and/or infectious mechanisms.

• #18 Castleman Disease: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/2219018-overview

  The etiologies differ between the four subtypes of Castleman disease. […] The etiology of UCD is unknown, but a subset of UCD cases may be the result of somatic mutations in monoclonal cell populations, likely lymph node stromal cells. Alternatively, UCD may occur due to exaggerations of the types of reactive changes that can be seen in response to normal antigenic stimuli. […] Active HHV-8 infection is the well-established etiology of HHV-8associated MCD. HHV-8 is a gamma herpesvirus similar to Epstein-Barr virus (EBV) that has been found in both endemic and HIV-associated Kaposi sarcoma (KS). The HHV-8 virus is pathologically responsible for all symptoms and signs of the disease. […] The etiology of HHV-8negative/idiopathic MCD (iMCD) is not known. The heterogeneity of clinical features and pathologic abnormalities, which overlap with a wide range of other immunologic disorders, suggests that multiple processes each involving immune dysregulation and a common pathway of increased cytokine levels may give rise to iMCD in different subsets of patients. Four candidate etiologic drivers of iMCD pathogenesis have been proposed: autoimmune, autoinflammatory, neoplastic, and/or infectious mechanisms.

• #19 Castleman Disease: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/2219018-overview

  The etiologies differ between the four subtypes of Castleman disease. […] The etiology of UCD is unknown, but a subset of UCD cases may be the result of somatic mutations in monoclonal cell populations, likely lymph node stromal cells. Alternatively, UCD may occur due to exaggerations of the types of reactive changes that can be seen in response to normal antigenic stimuli. […] Active HHV-8 infection is the well-established etiology of HHV-8associated MCD. HHV-8 is a gamma herpesvirus similar to Epstein-Barr virus (EBV) that has been found in both endemic and HIV-associated Kaposi sarcoma (KS). The HHV-8 virus is pathologically responsible for all symptoms and signs of the disease. […] The etiology of HHV-8negative/idiopathic MCD (iMCD) is not known. The heterogeneity of clinical features and pathologic abnormalities, which overlap with a wide range of other immunologic disorders, suggests that multiple processes each involving immune dysregulation and a common pathway of increased cytokine levels may give rise to iMCD in different subsets of patients. Four candidate etiologic drivers of iMCD pathogenesis have been proposed: autoimmune, autoinflammatory, neoplastic, and/or infectious mechanisms.

• #20 Overview – Castleman Disease Collaborative Network | CDCN

  https://cdcn.org/castleman-disease/overview/

  A small proportion of individuals infected with this virus, who are either HIV positive or have suppressed immune systems for another cause, develop HHV-8-associated MCD. In HHV-8+MCD, uncontrolled infection with HHV-8 causes the immune system to produce excessive cytokines that lead to MCD. […] The most common subtype of MCD is idiopathic multicentric Castleman disease (iMCD). Though iMCD patients experience excessive cytokine production and a cytokine storm, the cause is unknown. There is no evidence of POEMS, HHV-8, or any other cancer or infectious disease in these patients.

• #21 Overview – Castleman Disease Collaborative Network | CDCN

  https://cdcn.org/castleman-disease/overview/

  A small proportion of individuals infected with this virus, who are either HIV positive or have suppressed immune systems for another cause, develop HHV-8-associated MCD. In HHV-8+MCD, uncontrolled infection with HHV-8 causes the immune system to produce excessive cytokines that lead to MCD. […] The most common subtype of MCD is idiopathic multicentric Castleman disease (iMCD). Though iMCD patients experience excessive cytokine production and a cytokine storm, the cause is unknown. There is no evidence of POEMS, HHV-8, or any other cancer or infectious disease in these patients.

• #22 Castleman Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK576394/

  Castleman disease is a lymphoproliferative disorder with a nondefinite etiology and can be classified into subtypes based on clinical and histological manifestations. […] There is very little knowledge available about the etiology of this disorder, but some evidence that has been collected claims it to be a result of impaired immunoregulation that causes abundant proliferation of B lymphocytes and plasma cells in lymphoid organs. These conditions can result from chronic low-grade inflammation, lymphoid-hamartomatous hyperplasia, viral infections, abnormal modulation of cytokines, and angiogenesis. […] In addition, a very close association of the disease with HIV has been discovered, which puts immunodeficiency on the list as well. Particularly in MCD, the causative factors include human herpesvirus (HHV)-8, which causes deregulation of the inflammatory mediators like CD20 and interleukin (IL)-6. […] Almost all cases of HIV-associated Castleman disease are HHV-8 positive, compared to 40 to 50% of non-HIV CD. The remaining cases unrelated to HIV or HHV-8, termed idiopathic multicentric CD (iMCD), have no established etiology to date.

• #23 Castleman Disease Causes, Symptoms, Risk Factors, Diagnosis and Treatment

  https://www.prepladder.com/neet-pg-study-material/pathology/castleman-disease-causes-symptoms-risk-factors-diagnosis-and-treatment

  Castleman disease is a rare condition caused by an excess of cells in your body’s lymph nodes. The most common variant of the illness affects a single lymph node, usually in the abdomen or chest. The medical term for this variation is unicentric Castleman disease. […] It is uncertain what causes Castleman’s illness. However, infection with the human herpes virus 8, or HHV-8, is connected to multicentric Castleman sickness. […] Research shows that HHV-8 is found in nearly all HIV-positive patients with Castleman disease and less than half of HIV-negative patients with the illness.

• #24 Castleman Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK576394/

  Castleman disease is a lymphoproliferative disorder with a nondefinite etiology and can be classified into subtypes based on clinical and histological manifestations. […] There is very little knowledge available about the etiology of this disorder, but some evidence that has been collected claims it to be a result of impaired immunoregulation that causes abundant proliferation of B lymphocytes and plasma cells in lymphoid organs. These conditions can result from chronic low-grade inflammation, lymphoid-hamartomatous hyperplasia, viral infections, abnormal modulation of cytokines, and angiogenesis. […] In addition, a very close association of the disease with HIV has been discovered, which puts immunodeficiency on the list as well. Particularly in MCD, the causative factors include human herpesvirus (HHV)-8, which causes deregulation of the inflammatory mediators like CD20 and interleukin (IL)-6. […] Almost all cases of HIV-associated Castleman disease are HHV-8 positive, compared to 40 to 50% of non-HIV CD. The remaining cases unrelated to HIV or HHV-8, termed idiopathic multicentric CD (iMCD), have no established etiology to date.

• #25 Castleman’s disease—a two compartment model of HHV8 infection | Nature Reviews Clinical Oncology

  https://www.nature.com/articles/nrclinonc.2010.103

  Castleman’s disease is a primary infectious disease of the lymph node that causes local symptoms or a systemic inflammatory syndrome. […] Viral interleukin 6 (vIL-6) produced during the replication of human herpesvirus type 8 (HHV8) is the key driver of systemic inflammation and cellular proliferation. […] Infection by human herpesvirus type 8 drives systemic inflammation and cellular proliferation via viral interleukin-6 (vIL-6). Complementing HIV infection always induces multicentric plasma cell disease. […] Infection is propagated in two cellular compartments: lymphovascular endothelial cells and plasma cell precursors. They differ in proliferation dynamics and vIL-6 production resulting in pleiomorphic pathological and clinical presentations.

• #26 Castleman’s disease—a two compartment model of HHV8 infection | Nature Reviews Clinical Oncology

  https://www.nature.com/articles/nrclinonc.2010.103

  Castleman’s disease is a primary infectious disease of the lymph node that causes local symptoms or a systemic inflammatory syndrome. […] Viral interleukin 6 (vIL-6) produced during the replication of human herpesvirus type 8 (HHV8) is the key driver of systemic inflammation and cellular proliferation. […] Infection by human herpesvirus type 8 drives systemic inflammation and cellular proliferation via viral interleukin-6 (vIL-6). Complementing HIV infection always induces multicentric plasma cell disease. […] Infection is propagated in two cellular compartments: lymphovascular endothelial cells and plasma cell precursors. They differ in proliferation dynamics and vIL-6 production resulting in pleiomorphic pathological and clinical presentations.

• #27 Overview – Castleman Disease Collaborative Network | CDCN

  https://cdcn.org/castleman-disease/overview/

  Castleman disease (CD) describes a group of rare disorders that involve enlarged lymph nodes with a similar lymph node appearance under the microscope and a broad range of inflammatory symptoms and laboratory abnormalities. […] Whether Castleman disease should be considered an autoimmune disease, cancer, or infectious disease is currently unknown. […] MCD is further sub-classified based on the underlying cause: POEMS-associated MCD, HHV-8-associated multicentric Castleman disease and idiopathic multicentric Castleman disease (iMCD). […] POEMS-associated MCD involves a cancerous cell population found in patients with POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes) that can cause excessive cytokine production and MCD in a fraction of patients.

• #28 Cutaneous Disorders Associated with Castleman’s Disease | HTML | Acta Dermato-Venereologica

  https://www.medicaljournals.se/acta/content/html/10.2340/00015555-3253

  In idiopathic MCD, elevated levels of IL-6 are also observed, which may be related to disease flares. […] IL-6 is a key mediator in the pathogenesis of MCD. […] PV-type CD and MCD show more frequent systemic complications than do HV-type CD and UCD due to increased IL-6. […] Thus, MCD predominated clinically and PV-type CD predominated pathologically in patients with CD with a cutaneous disorder, unlike that in patients with CD without a cutaneous disorder. […] Given the above-noted previous research, we classified PNP and xanthoma as immunological (antibody)-related cutaneous manifestations. […] POEMS-associated MCD is thought to be caused by cytokine production from monoclonal plasma cells that have undergone genomic events, such as translocations or deletions. […] Therefore, we sub-classified the 5 cases of vasculitis, angioma, hyperpigmentation into the same category based on their cytokine-related mechanisms.

• #29 Overview – Castleman Disease Collaborative Network | CDCN

  https://cdcn.org/castleman-disease/overview/

  A small proportion of individuals infected with this virus, who are either HIV positive or have suppressed immune systems for another cause, develop HHV-8-associated MCD. In HHV-8+MCD, uncontrolled infection with HHV-8 causes the immune system to produce excessive cytokines that lead to MCD. […] The most common subtype of MCD is idiopathic multicentric Castleman disease (iMCD). Though iMCD patients experience excessive cytokine production and a cytokine storm, the cause is unknown. There is no evidence of POEMS, HHV-8, or any other cancer or infectious disease in these patients.

• #30 Overview – Castleman Disease Collaborative Network | CDCN

  https://cdcn.org/castleman-disease/overview/

  A small proportion of individuals infected with this virus, who are either HIV positive or have suppressed immune systems for another cause, develop HHV-8-associated MCD. In HHV-8+MCD, uncontrolled infection with HHV-8 causes the immune system to produce excessive cytokines that lead to MCD. […] The most common subtype of MCD is idiopathic multicentric Castleman disease (iMCD). Though iMCD patients experience excessive cytokine production and a cytokine storm, the cause is unknown. There is no evidence of POEMS, HHV-8, or any other cancer or infectious disease in these patients.

• #31 Idiopathic Multicentric Castleman Disease (iMCD) – Rare Awareness Rare Education

  https://rareportal.org.au/rare-disease/idiopathic-multicentric-castleman-disease-imcd/

  Idiopathic multicentric Castleman disease (iMCD) is a type of Castleman disease where multiple lymph nodes throughout the body become enlarged and overactive, for an unknown reason. […] The cause of idiopathic multicentric Castleman disease (iMCD) is unknown. There are no known risk factors.

• #32 Overview – Castleman Disease Collaborative Network | CDCN

  https://cdcn.org/castleman-disease/overview/

  A small proportion of individuals infected with this virus, who are either HIV positive or have suppressed immune systems for another cause, develop HHV-8-associated MCD. In HHV-8+MCD, uncontrolled infection with HHV-8 causes the immune system to produce excessive cytokines that lead to MCD. […] The most common subtype of MCD is idiopathic multicentric Castleman disease (iMCD). Though iMCD patients experience excessive cytokine production and a cytokine storm, the cause is unknown. There is no evidence of POEMS, HHV-8, or any other cancer or infectious disease in these patients.

• #33 Castleman Disease: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/2219018-overview

  The etiologies differ between the four subtypes of Castleman disease. […] The etiology of UCD is unknown, but a subset of UCD cases may be the result of somatic mutations in monoclonal cell populations, likely lymph node stromal cells. Alternatively, UCD may occur due to exaggerations of the types of reactive changes that can be seen in response to normal antigenic stimuli. […] Active HHV-8 infection is the well-established etiology of HHV-8associated MCD. HHV-8 is a gamma herpesvirus similar to Epstein-Barr virus (EBV) that has been found in both endemic and HIV-associated Kaposi sarcoma (KS). The HHV-8 virus is pathologically responsible for all symptoms and signs of the disease. […] The etiology of HHV-8negative/idiopathic MCD (iMCD) is not known. The heterogeneity of clinical features and pathologic abnormalities, which overlap with a wide range of other immunologic disorders, suggests that multiple processes each involving immune dysregulation and a common pathway of increased cytokine levels may give rise to iMCD in different subsets of patients. Four candidate etiologic drivers of iMCD pathogenesis have been proposed: autoimmune, autoinflammatory, neoplastic, and/or infectious mechanisms.

• #34 Castleman Disease: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/2219018-overview

  The etiologies differ between the four subtypes of Castleman disease. […] The etiology of UCD is unknown, but a subset of UCD cases may be the result of somatic mutations in monoclonal cell populations, likely lymph node stromal cells. Alternatively, UCD may occur due to exaggerations of the types of reactive changes that can be seen in response to normal antigenic stimuli. […] Active HHV-8 infection is the well-established etiology of HHV-8associated MCD. HHV-8 is a gamma herpesvirus similar to Epstein-Barr virus (EBV) that has been found in both endemic and HIV-associated Kaposi sarcoma (KS). The HHV-8 virus is pathologically responsible for all symptoms and signs of the disease. […] The etiology of HHV-8negative/idiopathic MCD (iMCD) is not known. The heterogeneity of clinical features and pathologic abnormalities, which overlap with a wide range of other immunologic disorders, suggests that multiple processes each involving immune dysregulation and a common pathway of increased cytokine levels may give rise to iMCD in different subsets of patients. Four candidate etiologic drivers of iMCD pathogenesis have been proposed: autoimmune, autoinflammatory, neoplastic, and/or infectious mechanisms.

• #35 Idiopathic multicentric Castleman disease – Wikipedia

  https://en.wikipedia.org/wiki/Idiopathic_multicentric_Castleman_disease

  The cause of iMCD is not known and no risk factors have been identified. […] Genetic variants have been observed in cases of Castleman disease; however, no genetic variant has been validated as disease causing. […] Unlike HHV-8-associated MCD, iMCD is not caused by uncontrolled HHV-8 infection. […] The disease mechanism of iMCD has not been fully described. It is known that interleukin-6 (IL-6), a molecule that stimulates immune cells, plays a role in some cases of iMCD. […] Several theoretical mechanisms for iMCD have been proposed based on existing research and observed similarities between iMCD and other diseases that present with similar clinical findings and lymph node histology: Autoimmune The immune system may produce antibodies that target healthy cells in the body instead of bacteria and viruses.

• #36 Idiopathic multicentric Castleman disease – Wikipedia

  https://en.wikipedia.org/wiki/Idiopathic_multicentric_Castleman_disease

  Autoinflammatory A mutation in a gene controlling inflammatory systems may contribute to harmful activation of inflammatory pathways in patients with iMCD. […] Neoplastic Genetic mutations that develop in mature cells (somatic mutations) may cause an overgrowth of abnormal cells as in cancers such as lymphoma. […] Pathogen Human herpesvirus 8 (HHV-8) is the known causative agent in HHV-8-associated MCD, which has very similar symptoms and findings to iMCD. While iMCD by definition is not caused by HHV-8, an unknown virus may cause the disease.

• #37 Castleman Disease: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/2219018-overview

  There are at least three clinical subgroups of iMCD that may each arise from different etiologies than those proposed above: […] TAFRO syndrome, HHV-8negative/idiopathic MCD (iMCD-TAFRO): Thrombocytopenia, anasarca, fever, myelofibrosis, renal dysfunction or reticulin fibrosis, and organomegaly (TAFRO) often occurs in HHV-8negative MCD. These cases often have mixed or hypervascular (formerly called hyaline vascular) histopathologic features and normal gamma globulin levels. The etiology and pathological cell types are unknown. […] iMCD with idiopathic plasmacytic lymphadenopathy (iMCD-IPL): These patients often have thrombocytosis, hypergammaglobulinemia, mixed or plasmacytic histopathological features, and a more chronic disease course. The etiology and pathological cell types are unknown. […] Not otherwise specified (NOS), HHV-8negative/idiopathic MCD (iMCD-NOS): HHV-8negative MCD patients who do not have iMCD-TAFRO or iMCD-IPL are considered to have iMCD-NOS. The etiology and pathological cell types are unknown.

• #38 Castleman Disease: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/2219018-overview

  There are at least three clinical subgroups of iMCD that may each arise from different etiologies than those proposed above: […] TAFRO syndrome, HHV-8negative/idiopathic MCD (iMCD-TAFRO): Thrombocytopenia, anasarca, fever, myelofibrosis, renal dysfunction or reticulin fibrosis, and organomegaly (TAFRO) often occurs in HHV-8negative MCD. These cases often have mixed or hypervascular (formerly called hyaline vascular) histopathologic features and normal gamma globulin levels. The etiology and pathological cell types are unknown. […] iMCD with idiopathic plasmacytic lymphadenopathy (iMCD-IPL): These patients often have thrombocytosis, hypergammaglobulinemia, mixed or plasmacytic histopathological features, and a more chronic disease course. The etiology and pathological cell types are unknown. […] Not otherwise specified (NOS), HHV-8negative/idiopathic MCD (iMCD-NOS): HHV-8negative MCD patients who do not have iMCD-TAFRO or iMCD-IPL are considered to have iMCD-NOS. The etiology and pathological cell types are unknown.

• #39 Castleman Disease: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/2219018-overview

  There are at least three clinical subgroups of iMCD that may each arise from different etiologies than those proposed above: […] TAFRO syndrome, HHV-8negative/idiopathic MCD (iMCD-TAFRO): Thrombocytopenia, anasarca, fever, myelofibrosis, renal dysfunction or reticulin fibrosis, and organomegaly (TAFRO) often occurs in HHV-8negative MCD. These cases often have mixed or hypervascular (formerly called hyaline vascular) histopathologic features and normal gamma globulin levels. The etiology and pathological cell types are unknown. […] iMCD with idiopathic plasmacytic lymphadenopathy (iMCD-IPL): These patients often have thrombocytosis, hypergammaglobulinemia, mixed or plasmacytic histopathological features, and a more chronic disease course. The etiology and pathological cell types are unknown. […] Not otherwise specified (NOS), HHV-8negative/idiopathic MCD (iMCD-NOS): HHV-8negative MCD patients who do not have iMCD-TAFRO or iMCD-IPL are considered to have iMCD-NOS. The etiology and pathological cell types are unknown.

• #40 Castleman Disease: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/2219018-overview

  There are at least three clinical subgroups of iMCD that may each arise from different etiologies than those proposed above: […] TAFRO syndrome, HHV-8negative/idiopathic MCD (iMCD-TAFRO): Thrombocytopenia, anasarca, fever, myelofibrosis, renal dysfunction or reticulin fibrosis, and organomegaly (TAFRO) often occurs in HHV-8negative MCD. These cases often have mixed or hypervascular (formerly called hyaline vascular) histopathologic features and normal gamma globulin levels. The etiology and pathological cell types are unknown. […] iMCD with idiopathic plasmacytic lymphadenopathy (iMCD-IPL): These patients often have thrombocytosis, hypergammaglobulinemia, mixed or plasmacytic histopathological features, and a more chronic disease course. The etiology and pathological cell types are unknown. […] Not otherwise specified (NOS), HHV-8negative/idiopathic MCD (iMCD-NOS): HHV-8negative MCD patients who do not have iMCD-TAFRO or iMCD-IPL are considered to have iMCD-NOS. The etiology and pathological cell types are unknown.

• #41

  https://haematologica.org/article/view/haematol.2021.280370

  Castleman disease is a polyclonal lymphoproliferative disorder characterized by unicentric or multicentric lymphadenopathy with characteristic histomorphological features, in addition to variable inflammatory symptomatology. […] The molecular mechanisms and etiologies of unicentric Castleman disease (UCD) and idiopathic multicentric Castleman disease (iMCD) are poorly understood, and identification of targetable disease mediators remains an unmet clinical need. […] The cellular and molecular mechanisms of UCD and iMCD are poorly understood. Most evidence points to an inflammatory process mediated by interleukin (IL)-6, vascular endothelial growth factor (VEGF) and/or chemokines in iMCD, compared to a lymphoproliferative process likely mediated by dysregulated lymph node stromal cells in UCD. However, the etiology of these processes is completely unknown.

• #42

  https://haematologica.org/article/view/haematol.2021.280370

  Castleman disease is a polyclonal lymphoproliferative disorder characterized by unicentric or multicentric lymphadenopathy with characteristic histomorphological features, in addition to variable inflammatory symptomatology. […] The molecular mechanisms and etiologies of unicentric Castleman disease (UCD) and idiopathic multicentric Castleman disease (iMCD) are poorly understood, and identification of targetable disease mediators remains an unmet clinical need. […] The cellular and molecular mechanisms of UCD and iMCD are poorly understood. Most evidence points to an inflammatory process mediated by interleukin (IL)-6, vascular endothelial growth factor (VEGF) and/or chemokines in iMCD, compared to a lymphoproliferative process likely mediated by dysregulated lymph node stromal cells in UCD. However, the etiology of these processes is completely unknown.

• #43 Cutaneous Disorders Associated with Castleman’s Disease | HTML | Acta Dermato-Venereologica

  https://www.medicaljournals.se/acta/content/html/10.2340/00015555-3253

  In idiopathic MCD, elevated levels of IL-6 are also observed, which may be related to disease flares. […] IL-6 is a key mediator in the pathogenesis of MCD. […] PV-type CD and MCD show more frequent systemic complications than do HV-type CD and UCD due to increased IL-6. […] Thus, MCD predominated clinically and PV-type CD predominated pathologically in patients with CD with a cutaneous disorder, unlike that in patients with CD without a cutaneous disorder. […] Given the above-noted previous research, we classified PNP and xanthoma as immunological (antibody)-related cutaneous manifestations. […] POEMS-associated MCD is thought to be caused by cytokine production from monoclonal plasma cells that have undergone genomic events, such as translocations or deletions. […] Therefore, we sub-classified the 5 cases of vasculitis, angioma, hyperpigmentation into the same category based on their cytokine-related mechanisms.

• #44 Cutaneous Disorders Associated with Castleman’s Disease | HTML | Acta Dermato-Venereologica

  https://www.medicaljournals.se/acta/content/html/10.2340/00015555-3253

  In idiopathic MCD, elevated levels of IL-6 are also observed, which may be related to disease flares. […] IL-6 is a key mediator in the pathogenesis of MCD. […] PV-type CD and MCD show more frequent systemic complications than do HV-type CD and UCD due to increased IL-6. […] Thus, MCD predominated clinically and PV-type CD predominated pathologically in patients with CD with a cutaneous disorder, unlike that in patients with CD without a cutaneous disorder. […] Given the above-noted previous research, we classified PNP and xanthoma as immunological (antibody)-related cutaneous manifestations. […] POEMS-associated MCD is thought to be caused by cytokine production from monoclonal plasma cells that have undergone genomic events, such as translocations or deletions. […] Therefore, we sub-classified the 5 cases of vasculitis, angioma, hyperpigmentation into the same category based on their cytokine-related mechanisms.

• #45 Characteristics of Castleman’s Disease

  https://www.targetedonc.com/view/characteristics-of-castlemans-disease

  Castleman’s disease is a fascinating disease with a number of different things that we think can lead to its genesis. The pathogenesis of the disease is interesting and probably accounts for the diverse clinical manifestations. The way I think about Castleman’s disease is that the central property of the disease is that you have an overexpression of interleukin-6 (IL-6). Interleukin-6 is a cytokine that has a number of different effects, but it certainly calls for the recruitment and expansion of B-cells and plasma cells, the enlargement of lymph nodes, and a series of constitutional symptoms when interleukin-6 is overexpressed. That is a central feature of all forms of Castleman’s disease. Now, what causes the interleukin-6 to be elevated has many different potential sources. […] One source that we clearly understand is that there is a virus, a virus known as human herpesvirus 8. This virus makes an analog to interleukin-6 that is called viral interleukin-6. It shares about 40% homology with the protein, and, indeed, the overexpression of that viral interleukin-6 causes also an overexpression of human interleukin-6. Together they cause the symptoms of Castleman’s disease. There may well be other viruses that have a similar mechanism, but that hasn’t been elucidated. So, for right now, we know that that’s one mechanism of Castleman’s disease.

• #46 Characteristics of Castleman’s Disease

  https://www.targetedonc.com/view/characteristics-of-castlemans-disease

  For the other cases of Castleman’s disease that are not related to the virus, we tend to call those idiopathic multicentric Castleman’s disease or disease that we don’t really know what the etiology is. For those, there’s an increasing understanding of some of the factors that may contribute. For instance, we know that there are promoter polymorphisms for the IL-6 gene that lead to constitutive overexpression of IL-6 protein. Patients have either constant production of IL-6 or an exaggerated response to producing IL-6 when they should only produce a little bit of it. So, that again is an overproduction of IL-6 from a genetic polymorphism. Whether you’re born with that or that accumulates over the course of your life, we don’t know. There haven’t really been families or kindreds where Castleman’s disease runs in the family, but there are suggestions that there are families that have a higher prevalence of autoimmune diseases, lymphomas, and other inflammatory diseases, even cases like multiple sclerosis where they will also have histories of Castleman’s disease.

• #47 Characteristics of Castleman’s Disease

  https://www.targetedonc.com/view/characteristics-of-castlemans-disease

  So, I guess, in my mind, I think about cases where IL-6 is overexpressed because of a virus and we know that’s human herpesvirus-8, but there may be others. We know that there are genetic polymorphisms that lead to too much IL-6 production, and I would imagine that as we learn more about this disease and learn more about the IL-6 pathway, there may be other factors downstream of the receptor signaling within cell signaling pathways that could be mutated and lead to the same phenotype of IL-6 overexpression.

• #48 Characteristics of Castleman’s Disease

  https://www.targetedonc.com/view/characteristics-of-castlemans-disease

  For the other cases of Castleman’s disease that are not related to the virus, we tend to call those idiopathic multicentric Castleman’s disease or disease that we don’t really know what the etiology is. For those, there’s an increasing understanding of some of the factors that may contribute. For instance, we know that there are promoter polymorphisms for the IL-6 gene that lead to constitutive overexpression of IL-6 protein. Patients have either constant production of IL-6 or an exaggerated response to producing IL-6 when they should only produce a little bit of it. So, that again is an overproduction of IL-6 from a genetic polymorphism. Whether you’re born with that or that accumulates over the course of your life, we don’t know. There haven’t really been families or kindreds where Castleman’s disease runs in the family, but there are suggestions that there are families that have a higher prevalence of autoimmune diseases, lymphomas, and other inflammatory diseases, even cases like multiple sclerosis where they will also have histories of Castleman’s disease.

• #49

  https://haematologica.org/article/view/haematol.2021.280370

  A few studies have demonstrated the presence of low allele frequency, gene mutations and/or chromosomal abnormalities in a subset of patients with Castleman disease, suggestive of a low-level clonal proliferative process most likely within the stromal cell component. […] We demonstrate that the transcriptomes of both UCD and iMCD are enriched for elements of the complement cascade. […] The increased transcription of complement-related genes in Castleman lymphadenopathy and evidence of complement activation within the characteristically abnormal germinal centers raise the possibility of complement activation as a possible mediator of the inflammatory manifestations of UCD and iMCD. […] We did not find increased IL6 transcripts on lymph nodes from patients with Castleman disease, compared to controls. This finding was unexpected, as the inflammatory manifestations of Castleman disease are believed to be mediated at least in part by IL-6, based on several lines of evidence. […] Our findings suggest that a role may exist for PGF/FLT1 and APLN/APLNR signaling as intrinsic angiogenic mediators in lymph nodes involved by Castleman disease.

• #50

  https://haematologica.org/article/view/haematol.2021.280370

  A few studies have demonstrated the presence of low allele frequency, gene mutations and/or chromosomal abnormalities in a subset of patients with Castleman disease, suggestive of a low-level clonal proliferative process most likely within the stromal cell component. […] We demonstrate that the transcriptomes of both UCD and iMCD are enriched for elements of the complement cascade. […] The increased transcription of complement-related genes in Castleman lymphadenopathy and evidence of complement activation within the characteristically abnormal germinal centers raise the possibility of complement activation as a possible mediator of the inflammatory manifestations of UCD and iMCD. […] We did not find increased IL6 transcripts on lymph nodes from patients with Castleman disease, compared to controls. This finding was unexpected, as the inflammatory manifestations of Castleman disease are believed to be mediated at least in part by IL-6, based on several lines of evidence. […] Our findings suggest that a role may exist for PGF/FLT1 and APLN/APLNR signaling as intrinsic angiogenic mediators in lymph nodes involved by Castleman disease.

• #51

  https://www.xiahepublishing.com/2771-165X/JCTP-2024-00047

  Castleman disease (CD) is a lymphoproliferative condition with a broad range of morphological and clinical presentations. […] Additionally, individuals diagnosed with CD are at an elevated risk of developing various malignancies. […] Various malignancies are associated with CD, including plasma cell proliferations, lymphomas, follicular dendritic cell neoplasms, and Kaposi sarcoma. […] Patients diagnosed with CD can also develop malignancies at a notably higher rate than the expected age-adjusted prevalence. […] A systematic literature review identified multiple hematologic malignancies associated with CD, including angioimmunoblastic T-cell lymphoma, mantle cell lymphoma, diffuse large B-cell lymphoma, Hodgkin lymphoma, acute myeloid leukemia, and multiple myeloma. […] Among the most frequent neoplasms linked to CD are hematolymphoid malignancies, Kaposi sarcoma, and FDC sarcoma.

• #52

  https://www.xiahepublishing.com/2771-165X/JCTP-2024-00047

  Castleman disease (CD) is a lymphoproliferative condition with a broad range of morphological and clinical presentations. […] Additionally, individuals diagnosed with CD are at an elevated risk of developing various malignancies. […] Various malignancies are associated with CD, including plasma cell proliferations, lymphomas, follicular dendritic cell neoplasms, and Kaposi sarcoma. […] Patients diagnosed with CD can also develop malignancies at a notably higher rate than the expected age-adjusted prevalence. […] A systematic literature review identified multiple hematologic malignancies associated with CD, including angioimmunoblastic T-cell lymphoma, mantle cell lymphoma, diffuse large B-cell lymphoma, Hodgkin lymphoma, acute myeloid leukemia, and multiple myeloma. […] Among the most frequent neoplasms linked to CD are hematolymphoid malignancies, Kaposi sarcoma, and FDC sarcoma.

• #53

  https://www.xiahepublishing.com/2771-165X/JCTP-2024-00047

  Castleman disease (CD) is a lymphoproliferative condition with a broad range of morphological and clinical presentations. […] Additionally, individuals diagnosed with CD are at an elevated risk of developing various malignancies. […] Various malignancies are associated with CD, including plasma cell proliferations, lymphomas, follicular dendritic cell neoplasms, and Kaposi sarcoma. […] Patients diagnosed with CD can also develop malignancies at a notably higher rate than the expected age-adjusted prevalence. […] A systematic literature review identified multiple hematologic malignancies associated with CD, including angioimmunoblastic T-cell lymphoma, mantle cell lymphoma, diffuse large B-cell lymphoma, Hodgkin lymphoma, acute myeloid leukemia, and multiple myeloma. […] Among the most frequent neoplasms linked to CD are hematolymphoid malignancies, Kaposi sarcoma, and FDC sarcoma.

• #54

  https://www.xiahepublishing.com/2771-165X/JCTP-2024-00047

  Castleman disease (CD) is a lymphoproliferative condition with a broad range of morphological and clinical presentations. […] Additionally, individuals diagnosed with CD are at an elevated risk of developing various malignancies. […] Various malignancies are associated with CD, including plasma cell proliferations, lymphomas, follicular dendritic cell neoplasms, and Kaposi sarcoma. […] Patients diagnosed with CD can also develop malignancies at a notably higher rate than the expected age-adjusted prevalence. […] A systematic literature review identified multiple hematologic malignancies associated with CD, including angioimmunoblastic T-cell lymphoma, mantle cell lymphoma, diffuse large B-cell lymphoma, Hodgkin lymphoma, acute myeloid leukemia, and multiple myeloma. […] Among the most frequent neoplasms linked to CD are hematolymphoid malignancies, Kaposi sarcoma, and FDC sarcoma.

• #55

  https://www.xiahepublishing.com/2771-165X/JCTP-2024-00047

  The most frequently observed hematolymphoid malignancies linked to CD include classic Hodgkin lymphoma, diffuse large B-cell lymphoma with or without HHV8 association, primary effusion lymphoma, mantle cell lymphoma, peripheral T-cell lymphoma, and plasma cell neoplasms. […] There have also been documented cases of CD occurring concurrently with nasal-type natural killer/T-cell lymphoma, particularly in patients with EBV and HHV-8 co-infection. […] Studies suggest that CD is a clonal neoplastic process, with follicular dendritic cells likely representing the cell of origin.

• #56

  https://www.xiahepublishing.com/2771-165X/JCTP-2024-00047

  The most frequently observed hematolymphoid malignancies linked to CD include classic Hodgkin lymphoma, diffuse large B-cell lymphoma with or without HHV8 association, primary effusion lymphoma, mantle cell lymphoma, peripheral T-cell lymphoma, and plasma cell neoplasms. […] There have also been documented cases of CD occurring concurrently with nasal-type natural killer/T-cell lymphoma, particularly in patients with EBV and HHV-8 co-infection. […] Studies suggest that CD is a clonal neoplastic process, with follicular dendritic cells likely representing the cell of origin.

• #57

  https://www.xiahepublishing.com/2771-165X/JCTP-2024-00047

  The most frequently observed hematolymphoid malignancies linked to CD include classic Hodgkin lymphoma, diffuse large B-cell lymphoma with or without HHV8 association, primary effusion lymphoma, mantle cell lymphoma, peripheral T-cell lymphoma, and plasma cell neoplasms. […] There have also been documented cases of CD occurring concurrently with nasal-type natural killer/T-cell lymphoma, particularly in patients with EBV and HHV-8 co-infection. […] Studies suggest that CD is a clonal neoplastic process, with follicular dendritic cells likely representing the cell of origin.

• #58 Castleman disease // Middlesex Health

  https://middlesexhealth.org/6D45E88A-F751-989D-073B9A57D2251060

  It’s not clear what causes unicentric Castleman disease or idiopathic multicentric Castleman disease (MCD). However, HHV-8-positive MCD is known to occur in people who don’t have typical function in their immune systems because of HIV or other causes. […] There are no known risk factors for unicentric Castleman disease or idiopathic multicentric Castleman disease. Infection with HIV or having a condition that decreases how well the immune system works raises the risk of having HHV-8-positive multicentric Castleman disease.

• #59 About Castleman Disease – Castleman Disease Collaborative Network

  https://cdcn.org/castleman-disease/

  Castleman disease (CD) is a group of three immune system disorders that share a similar lymph node appearance under the microscope, but have different symptoms, causes, and treatments. […] All cases of unicentric Castleman disease (UCD) and HHV-8-negative multicentric Castleman disease (iMCD) are idiopathic, which means that the cause is not known. There are also no known risk factors for UCD or iMCD, though the possibility of a genetic cause is being researched. In HHV-8-associated multicentric Castleman disease, the HHV-8 virus causes and drives the disease.

• #60 Castleman Disease | Condition | UAMS Health

  https://uamshealth.com/condition/castleman-disease/

  There are no known risk factors for UCD, POEMS-associated MCD, or iMCD; there is no evidence of any food, lifestyle, or environmental exposure associated with these diseases. […] The Myeloma Center participates with the Castleman Disease Collaborative Network to accelerate research and explore the causes of both unicentric and multicentric Castleman disease.

• #61 Castleman disease // Middlesex Health

  https://middlesexhealth.org/6D45E88A-F751-989D-073B9A57D2251060

  It’s not clear what causes unicentric Castleman disease or idiopathic multicentric Castleman disease (MCD). However, HHV-8-positive MCD is known to occur in people who don’t have typical function in their immune systems because of HIV or other causes. […] There are no known risk factors for unicentric Castleman disease or idiopathic multicentric Castleman disease. Infection with HIV or having a condition that decreases how well the immune system works raises the risk of having HHV-8-positive multicentric Castleman disease.

• #62 Castleman disease | City of Hope

  https://www.cancercenter.com/risk-factors/castleman-disease

  Castleman disease (CD) is a rare condition that affects the lymph nodes and related tissues. […] The exact cause of Castleman disease isnt known, and there are no known risk factors. Factors such as viruses, genetic mutations acquired over the course of life, an inherited genetic mutation, autoimmunity and inflammation may contribute to the disease. […] Recent research suggests that acquired genetic mutations seem to be the main cause of UCD, and some scientists theorize that an increased production of IL-6 by the immune system may contribute to the disease by causing an overgrowth of lymphatic cells, leading to many of the flu-like signs and other symptoms of CD. […] The HHV-8 present in many patients with MCD is also found in nearly all people who are HIV-positive. HIV weakens the immune systems ability to control the HHV-8 infection, and its thought that HHV-8 then causes MCD by making its own IL-6 and an overabundance of lymphatic cells.

• #63 What Is Multicentric Castleman Disease?

  https://www.healthline.com/health/multicentric-castleman-disease

  Multicentric Castleman disease can cause flu-like symptoms and raise the risk of cancer or serious infections. […] A 2023 study suggests that in one-third to one-half of all people with multicentric Castleman disease, the cause is unknown. […] Some research also suggests that human herpesvirus (HHV)-8 may lead to multicentric Castleman disease. This is known as HHV-8-associated multicentric Castleman disease. […] The only known risk factor for HHV-8-associated multicentric Castleman disease is having HIV. There are no established risk factors for idiopathic multicentric Castleman disease. […] Castleman disease can be a life threatening disease without prompt and effective treatment. Potential complications of the disease include severe damage to multiple organs and cancer.

• #64 What Is Multicentric Castleman Disease?

  https://www.healthline.com/health/multicentric-castleman-disease

  Multicentric Castleman disease can cause flu-like symptoms and raise the risk of cancer or serious infections. […] A 2023 study suggests that in one-third to one-half of all people with multicentric Castleman disease, the cause is unknown. […] Some research also suggests that human herpesvirus (HHV)-8 may lead to multicentric Castleman disease. This is known as HHV-8-associated multicentric Castleman disease. […] The only known risk factor for HHV-8-associated multicentric Castleman disease is having HIV. There are no established risk factors for idiopathic multicentric Castleman disease. […] Castleman disease can be a life threatening disease without prompt and effective treatment. Potential complications of the disease include severe damage to multiple organs and cancer.

• #65 Castleman Disease: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/2219018-overview

  The etiologies differ between the four subtypes of Castleman disease. […] The etiology of UCD is unknown, but a subset of UCD cases may be the result of somatic mutations in monoclonal cell populations, likely lymph node stromal cells. Alternatively, UCD may occur due to exaggerations of the types of reactive changes that can be seen in response to normal antigenic stimuli. […] Active HHV-8 infection is the well-established etiology of HHV-8associated MCD. HHV-8 is a gamma herpesvirus similar to Epstein-Barr virus (EBV) that has been found in both endemic and HIV-associated Kaposi sarcoma (KS). The HHV-8 virus is pathologically responsible for all symptoms and signs of the disease. […] The etiology of HHV-8negative/idiopathic MCD (iMCD) is not known. The heterogeneity of clinical features and pathologic abnormalities, which overlap with a wide range of other immunologic disorders, suggests that multiple processes each involving immune dysregulation and a common pathway of increased cytokine levels may give rise to iMCD in different subsets of patients. Four candidate etiologic drivers of iMCD pathogenesis have been proposed: autoimmune, autoinflammatory, neoplastic, and/or infectious mechanisms.

• #66 Pathology Outlines – Castleman disease

  https://www.pathologyoutlines.com/topic/lymphnodescastleman.html

  Etiopathogenesis remains not well known […] UCD: etiology is unclear […] iMCD: etiology is unclear […] HHV8 MCD: HHV8 infected endothelial cell proliferation and vascularization.

• #67 Castleman Disease: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/2219018-overview

  The etiologies differ between the four subtypes of Castleman disease. […] The etiology of UCD is unknown, but a subset of UCD cases may be the result of somatic mutations in monoclonal cell populations, likely lymph node stromal cells. Alternatively, UCD may occur due to exaggerations of the types of reactive changes that can be seen in response to normal antigenic stimuli. […] Active HHV-8 infection is the well-established etiology of HHV-8associated MCD. HHV-8 is a gamma herpesvirus similar to Epstein-Barr virus (EBV) that has been found in both endemic and HIV-associated Kaposi sarcoma (KS). The HHV-8 virus is pathologically responsible for all symptoms and signs of the disease. […] The etiology of HHV-8negative/idiopathic MCD (iMCD) is not known. The heterogeneity of clinical features and pathologic abnormalities, which overlap with a wide range of other immunologic disorders, suggests that multiple processes each involving immune dysregulation and a common pathway of increased cytokine levels may give rise to iMCD in different subsets of patients. Four candidate etiologic drivers of iMCD pathogenesis have been proposed: autoimmune, autoinflammatory, neoplastic, and/or infectious mechanisms.

• #68 Castleman disease – Wikipedia

  https://en.wikipedia.org/wiki/Castleman_disease

  Castleman disease describes a group of rare lymphoproliferative disorders that involve enlarged lymph nodes, and a broad range of inflammatory symptoms and laboratory abnormalities. Whether Castleman disease should be considered an autoimmune disease, cancer, or infectious disease is currently unknown. […] The exact cause of UCD is unknown, but appears to be due to a genetic change that occurs in the lymph node tissue, most similar to a benign tumor. […] A cancerous cell population found in patients with POEMS syndrome can cause MCD in a fraction of patients by producing cytokines that initiate a cytokine storm. […] HHV-8-associated MCD patients have multiple regions of enlarged lymph nodes and episodic inflammatory symptoms due to uncontrolled infection with HHV-8. […] Idiopathic multicentric Castleman disease (iMCD), which is the most common form of MCD, occurs for an unknown cause. There is no evidence of POEMS syndrome, HHV-8, or any other cancer or infectious disease.

• #69 Characteristics of Castleman’s Disease

  https://www.targetedonc.com/view/characteristics-of-castlemans-disease

  Castleman’s disease is a fascinating disease with a number of different things that we think can lead to its genesis. The pathogenesis of the disease is interesting and probably accounts for the diverse clinical manifestations. The way I think about Castleman’s disease is that the central property of the disease is that you have an overexpression of interleukin-6 (IL-6). Interleukin-6 is a cytokine that has a number of different effects, but it certainly calls for the recruitment and expansion of B-cells and plasma cells, the enlargement of lymph nodes, and a series of constitutional symptoms when interleukin-6 is overexpressed. That is a central feature of all forms of Castleman’s disease. Now, what causes the interleukin-6 to be elevated has many different potential sources. […] One source that we clearly understand is that there is a virus, a virus known as human herpesvirus 8. This virus makes an analog to interleukin-6 that is called viral interleukin-6. It shares about 40% homology with the protein, and, indeed, the overexpression of that viral interleukin-6 causes also an overexpression of human interleukin-6. Together they cause the symptoms of Castleman’s disease. There may well be other viruses that have a similar mechanism, but that hasn’t been elucidated. So, for right now, we know that that’s one mechanism of Castleman’s disease.

• #70 Castleman’s disease—a two compartment model of HHV8 infection | Nature Reviews Clinical Oncology

  https://www.nature.com/articles/nrclinonc.2010.103

  Castleman’s disease is a primary infectious disease of the lymph node that causes local symptoms or a systemic inflammatory syndrome. […] Viral interleukin 6 (vIL-6) produced during the replication of human herpesvirus type 8 (HHV8) is the key driver of systemic inflammation and cellular proliferation. […] Infection by human herpesvirus type 8 drives systemic inflammation and cellular proliferation via viral interleukin-6 (vIL-6). Complementing HIV infection always induces multicentric plasma cell disease. […] Infection is propagated in two cellular compartments: lymphovascular endothelial cells and plasma cell precursors. They differ in proliferation dynamics and vIL-6 production resulting in pleiomorphic pathological and clinical presentations.

• #71 Castleman Disease | Condition | UAMS Health

  https://uamshealth.com/condition/castleman-disease/

  There are no known risk factors for UCD, POEMS-associated MCD, or iMCD; there is no evidence of any food, lifestyle, or environmental exposure associated with these diseases. […] The Myeloma Center participates with the Castleman Disease Collaborative Network to accelerate research and explore the causes of both unicentric and multicentric Castleman disease.

Zobacz więcej