Castleman lymphoma D36.9

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 18.11.2021

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angiofollicular lymphnode hyperplasia; Castleman disease; Castleman tumor; Castleman tumor hyalinizing plasmacellular; giant lymphnode hyperplasia; hyalinizing plasmacellular; Lymph node hyperplasia

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Benjamin Castleman, 1954

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Castleman's lymphoma, also Castleman's disease, is a rare systemic disease defined by aetiologically as yet unexplained (HHV-8 infection?) hypertrophy of the lymph nodes with angio-follicular lymphoid hyperplasia.

Two forms of Castleman's lymphoma are distinguished:

  • the more frequent localized form (uCD) (about 400 cases have been described worldwide), in which only one lymph node is affected
  • the rarer multicentric form (mCD), in which several lymph nodes and lymph node stations are affected. This type is usually associated with HIV infection.

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< 2.4:1000,000/person in the general population.

In HIV-infected patients, the incidence is 4.3 cases per 10,000 patient-years according to a British study.

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An essential common feature of Castleman's disease is the overproduction of various cytokines, especially interleukin-6 (IL-6). Thus, the highly variable clinic of mCD is explained by the multiple effects of IL-6 on cells. IL-6 and other proinflammatory cytokines such as IL-10 induce proliferation of B cells and plasma cells, secretion of vascular endothelial growth factors, among others.

In HIV-associated Castleman disease, HHV-8 can be detected 100% of the time. The HHV-8 virus to increased production of a viral interleukin that induces effects similar to human IL-6. IL-6 and IL-10 are elevated in close association with HHV-8 viral load. Viral IL-6, unlike physiological human IL-6, only needs to bind to one of the two IL-6 receptor subunits to exert its effects. In this respect, it has broader leverage at the target cells and is thus likely to cause the disease-causing "cytokine storms" characteristic of HHV-8 MCD.

The pathogenesis of idiopathic mCD is more complex. Possible causes of cytokine overproduction include:

  • autoimmune mechanisms
  • ectopic secretion of cytokines by malignant cells
  • other associated viral infections
  • polymorphisms of the interleukin-6 receptor.

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There is neither an age nor a gender disposition.

Clinical features
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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.

Integument: tendency to severe infections and the increased occurrence of Kaposi's sarcoma, lymphoma and plasmocytoma. Furthermore POEMS-typical skin changes are found.

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.

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Histology: 3 types are distinguished:

  1. 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.
  2. 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.
  3. An intermediate type

Differential diagnosis
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Cutaneous and systemic plasmocytosis

Internal therapy
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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.

Cidofovir or ganciclovir was helpful in some HHV-8-positive patients were also cidofovir or ganciclovir.

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In the localized form of Castleman's disease, complete surgical excision leads to cure in 90% of all cases.

The prognosis of multicentric Castleman's disease is poor. In a study of HIV-infected patients, it averaged only 14 months.

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In the literature, overlaps between the plasma cell type of Castleman's disease and the"cutaneous and systemic plasmocytosis", which occurs preferentially in Asian countries, are discussed.

Castleman's lymphoma is disproportionately associated with paraneoplastic pemphigus.

Angiofollicular lymphoid hyperplasia is not a specific feature of Castleman disease, but is also seen in rheumatoid arthritis, Sjögren's syndrome, and congenital immunodeficiencies . Furthermore, this reaction occurs in malignancies, vaccinations and syphilis.

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  1. Bond SE (2003) Castleman's disease presenting as a midline neck mass. Br J Plast Surgery 56: 62-64
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  4. Castleman B, Inverson L, Pardo Menendez V (1956) Localized mediastinal lymphnode hyperplasia resembling thymoma. Cancer 9: 822-830
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  6. 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
  7. Fajgenbaum DC et al (2014) Eruptive cherry hemangiomatosis associated with multicentric Castleman disease: a case report and diagnostic clue. JAMA Dermatol 149:204-208.

  8. 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

  9. Hudnall SD et al (2003) Human herpesvirus-8 positive microvenular hemangioma in POEMS syndrome. Arch Catholic Lab Med 127: 1034-1036
  10. 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
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  12. 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

  13. 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.


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Last updated on: 18.11.2021