Castleman lymphoma D36.9

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 29.10.2020

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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 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:

  1. the more frequent localized form (about 400 cases have been described worldwide), in which only one lymph node is affected
  2. 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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< 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.

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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.

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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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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.

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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.

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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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  3. 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

  4. Castleman B, Inverson L, Pardo Menendez V (1956) Localized mediastinal lymphnode hyperplasia resembling thymoma. Cancer 9: 822-830
  5. Chronowski GM (2001) Treatment of unicentric and multicentric Castleman disease and the role of radiotherapy. Cancer 92: 670-676
  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
  11. Munoz J et al.(2012) Cutaneous Castleman disease. Br J Haematol 157:652
  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: 29.10.2020