Castleman disease (CD) is defined by lymph node hypertrophy with angiofollicular lymphoid hyperplasia. In the localised form, only one lymph node is affected, whereas several lymph nodes are involved in the multicentric form. The prevalence of the disease is unknown, but it has been estimated at less than 1/100 000. The localised form is the most frequent (more than 400 cases reported). The less common multicentric form may also occur in association with HIV infection. CD can occur at any age. The frequency of symptoms has been evaluated on a French cohort of 117 cases. Localised forms are asymptomatic in 51% of the patients and are often discovered fortuitously. They can sometimes cause chest or abdominal pain, when the lesion is large (mean diameter of 6 cm, with extremes ranging from 1 to 12 cm). The sites that are preferentially involved are, in decreasing order of frequency, the abdomen, the superficial lymph nodes and the mediastinum. Nonspecific signs, observed in 31% of the patients, include: asthenia (20%), fever (20%) and weight loss (11%). Multicentric forms are always symptomatic. Weight loss occurs in 69% of patients and fever in 67% of the cases. Peripheral lymphadenopathy is observed in 81% of the cases, hepatomegaly and/or splenomegaly in 74%, and POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes) in 23% of the patients. A few cases of Kaposi's sarcoma have also been described. The aetiology of CD remains unclear but several reports confirm the role of human herpes virus 8 (HHV-8), the causal agent of Kaposi's sarcoma. HHV8 was found in 60 to 100% of patients with HIV-associated CD, and also in 20 to 40% of HIV-negative patients. HHV8 is localised to immunoblasts and CD20+ lymph node B lymphocytes. HHV8 induces the production of a viral homologue of interleukin (vIL6), which could promote the occurrence of B lymphomas, such as primary effusion lymphomas. The diagnosis of CD requires lymph node histological analysis with immunohistochemical staining, showing polyclonal angiofollicular lymphoid hyperplasia, most often of the hyalinovascular type (especially in localised CD) and more rarely of the plasma-cell type (particularly in multicentric CD) or mixed/intermediate type. CD is typically a polyclonal lymphocytic proliferation, which should be distinguished from malignant lymphoma. Nevertheless, some cases of multicentric CD can be associated with lymphoma. Angiofollicular lymphoid hyperplasia is not a specific feature of CD and can be observed in rheumatoid arthritis, Sjögren syndrome, congenital immune deficiencies, reactions to cancers and hemopathies or vaccinations, syphilis, some cutaneous diseases or in membranous glomerulonephritis. These diseases should be ruled out before diagnosing a patient with CD. If CD is localised, a complete surgical excision needs to be performed; no follow-up is required. In multicentric CD, HIV and HHV-8 tests should first be carried out, as well as immunostaining to exclude lymphoma. Polychemotherapies such as the CHOP regimen (cyclophosphamide, doxorubicin, vincristine and prednisone) have been successful, but are associated with high toxicity; IFN-alpha, alone or in combination with vinblastine or etoposide, has proved beneficial; the anti-IL6 receptor antibody MRA can be used as an adjuvant therapy; retinoic acid has been successful in several patients; rituximab has given very promising results in HIV+ and HHV-8+ patients; cidofovir or ganciclovir were efficient in several HHV-8+ patients. In localised forms of CD, recovery without sequelae after complete surgical excision is reached in 90% of the cases. In multicentric forms, remission can be obtained, but relapse occurs in 25% of the patients and the prognosis is much less favourable.
Last update: November 2006
- Dr Françoise SARROT-REYNAULD