HistoryThis section has been translated automatically.
Benjamin Castleman, 1954
DefinitionThis section has been translated automatically.
Castleman lymphoma, also known as Castleman disease, is a rare systemic disease defined by an aetiologically as yet unexplained (HHV-8 infection?) hypertrophy of the lymph nodes with angio-follicular lymph hyperplasia.
Two forms of Castleman lymphoma are distinguished:
- the more frequent localized form (about 400 cases have been described worldwide), in which only one lymph node is affected
- the rarer multicentric form, in which several lymph nodes and lymph node stations are affected. This type is usually associated with HIV infection.
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Occurrence/EpidemiologyThis section has been translated automatically.
< 2.4:1000,000 per person in the general population; according to a British study, the incidence of HIV-infected patients is 4.3 cases per 10,000 patient-years.
EtiopathogenesisThis section has been translated automatically.
A major common feature of Castleman's disease is an overproduction of various cytokines, especially of interleukin-6 (IL-6). Thus, the highly variable clinic of MCD is explained by the manifold effects of IL-6 on cells. IL-6 and other proinflammatory cytokines such as IL-10 induce, among other things, proliferation of B cells and plasma cells, the secretion of vascular endothelial growth factors.
In HHV-8 positive cases, the HHV-8 virus leads to increased production of a viral interleukin that induces effects similar to those of human IL-6. IL-6 and IL-10 are elevated in close association with HHV-8 viral load. In contrast to the physiological human IL-6, viral IL-6 must bind to only one of the two IL-6 receptor subunits in order to exert its effect. In this respect, it has a broader leverage at the target cells and is thus likely to cause the "cytokine storms" that are characteristic of HHV-8 MCD and that cause disease.
The pathogenesis of idiopathic MCD is more complex. Possible causes of cytokine overproduction are: autoimmune mechanisms, ectopic secretion of cytokines by malignant cells, other associated viral infections, polymorphisms of the interleukin-6 receptor.
ManifestationThis section has been translated automatically.
There is neither an age nor a gender disposition.
Clinical featuresThis section has been translated automatically.
In the localized form, the lymph node regions of the abdomen, subcutaneous lymph nodes and mediastinal lymph nodes are particularly affected. The clinical picture is often defined by fatigue, fever, weight loss and undefinable chest or abdominal pain.
In the multi-centre form of the disease, weight loss (69%), fever (67%), peripheral lymphadenopathy (81%), hepato- and/or splenomegaly (74%) are observed, as well as POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes - eruptive "senile" angiomas) in about 20% of patients.
Less frequent are uncharacteristic exanthema as well as granulomatous and angiomatous skin manifestations (see glomeruloid hemangioma below) within the framework of the underlying disease.
In individual cases specific infiltrates are also found in the skin.
HistologyThis section has been translated automatically.
Histology: 3 types are distinguished:
- the more frequent hyaline-vascular type: in this type there is an uncontrolled proliferation of a clone of dendritic cells (clonal disease). The structure of the hyaline lymph nodes is "onion-skin-like". This form usually occurs locally.
- The rarer plasma-cell-rich type: this is usually observed in connection with HIV disease. It occurs multifocally and is based on an increased expression of interleukin 6 (IL-6) with a reactive proliferation of plasma cells.
- An intermediate type
Differential diagnosisThis section has been translated automatically.
Cutaneous and systemic plasmocytosis
Internal therapyThis section has been translated automatically.
Surgical removal: In the localized form of Castleman's disease, complete surgical removal leads to healing in 90% of all cases.
Chemotherapy: CHOP regimen (cyclophosphamide, doxorubicin, vincristine, prednisone)
Alternative: IFN-alpha alone or combined with vinblastine or etoposide
Adjuvant: an anti-IL6 receptor antibody (Siltuximab) may be used. Siltuximab has been approved since 2014 as the first drug for the treatment of idiopathic MCD and has not been tested in HHV-8 MCD because it is unlikely to bind to viral IL-6.
Rituximab: a monoclonal antibody against CD20, has been shown to be effective in HHV-8-MCD in several case series.
Progression/forecastThis section has been translated automatically.
With the localized form of M. Castleman, complete surgical removal leads to healing in 90% of all cases.
The prognosis for the multicenter M. Castleman is poor. In a study of HIV-infected patients it was only 14 months on average.
Note(s)This section has been translated automatically.
In the literature, overlaps between the plasmacellular type of Castleman's lymphoma and the"cutaneous and systemic plasmocytosis", which occurs mainly in Asian countries, are discussed.
Castleman's lymphoma is associated with paraneoplastic pemphigus with above-average frequency.
Angiofollicular lymphatic hyperplasia is not a specific feature of Castleman's disease, but is also seen in rheumatoid arthritis, Sjögren's syndrome and congenital immunodeficiencies. It also occurs in malignancies, vaccinations and syphilis.
LiteratureThis section has been translated automatically.
- Bond SE (2003) Castleman's disease presenting as a midline neck mass. Br J Plast Surgery 56: 62-64
Bower M et al (2014) Diagnostic criteria schemes for multicentric Castleman disease in 75 cases. J Acquir Immune Defic Syndr 65:e80-82.
Browne WB, Lewis J, Filippa DA et al (1999) The management of unicentric Castleman`s disease: a report of 16 cases and a review of the literature. Cancer 85: 706-717
- Castleman B, Inverson L, Pardo Menendez V (1956) Localized mediastinal lymphnode hyperplasia resembling thymoma. Cancer 9: 822-830
- Chronowski GM (2001) Treatment of unicentric and multicentric Castleman disease and the role of radiotherapy. Cancer 92: 670-676
- Dupin N (2000) HHV-8 is associated with a plasmablastic variant of Castleman disease that is linked to HHV-8 positive plasmablastic lymphoma. Blood 95: 1406-1412
Fajgenbaum DC et al (2014) Eruptive cherry hemangiomatosis associated with multicentric Castleman disease: a case report and diagnostic clue. JAMA Dermatol 149:204-208.
Hengge UR (2002) Update on Kaposi's sarcoma and other HHV8 associated diseases. Part 2: pathogenesis, Castleman's disease, and pleural effusion lymphoma. Lancet Infect Dis 2: 344-352
- Hudnall SD et al (2003) Human herpesvirus-8 positive microvenular hemangioma in POEMS syndrome. Arch Catholic Lab Med 127: 1034-1036
- Menke DM et al (2002) Analysis of the human herpesvirus 8 (HHV-8) genome and HHV-8 vIL-6 expression in archival cases of castleman disease at low risk for HIV infection. Am J Clin Pathol 117: 268-275
- Munoz J et al.(2012) Cutaneous Castleman disease. Br J Haematol 157:652
Polizzotto MN et al (2013) Human and viral interleukin-6 and other cytokines in Kaposi sarcoma herpesvirus-associated multicentric Castleman disease. Blood 122:4189-4198
Powles T et al (2009) The role of immune suppression and HHV-8 in the increasing incidence of HIV-associated multicentric Castleman's disease. Ann Oncol 20:775-779.
Incoming links (8)Angiofollicular lymphnode hyperplasia; Castleman tumor, hyalinizing plasmacellular; Cherry angioma; Giant lymphnode hyperplasia; HHV-8; Lymph node hyperplasia; Pemphigus paraneoplastic; Plasma cytosis cutaneous and systemic;
Outgoing links (10)Cherry angioma; Cidofovir; Ganciclovir; Hemangioma glomeruloides; Hiv infection; Kaposi's sarcoma (overview); Pemphigus paraneoplastic; Plasma cytosis cutaneous and systemic; Poems syndrome; Rituximab;
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