Castleman's disease

Castleman's disease (giant or angiofollicular lymph node hyperplasia) is a very rare disorder characterized by non-cancerous growths (tumors) that may develop in the lymph node tissue at a single site or throughout the body. It involves hyperproliferation of certain B cells that often produce cytokines. While not officially considered a cancer, the overgrowth of lymphocytes with this disease is similar to lymphoma.

It is named for Benjamin Castleman.

Types
There are several variants of Castleman's disease.

In all cases, Castleman's disease is likely due to hypersecretion of the cytokine IL-6.


 * In tumors that are positive for Kaposi's sarcoma-associated herpesvirus (KSHV), also called human herpes virus 8 (HHV-8), this is most likely due to expression of the virus-encoded cytokine, vIL-6.
 * KSHV negative tumors appear to be the result of over-secretion of human IL-6.

Unicentric vs. multicentric
Unicentric Castleman's disease involves tissue growths at only a single site. It usually has few or no symptoms other than those directly associated with the physical enlargement of the lymph node. In 90% or more, removal of the enlarged node is curative, with no further complications.

Multicentric Castleman's disease (MCD) involves growths at multiple sites. About 50% is caused by KSHV, also called HHV-8, a gammaherpesvirus that is also the cause of Kaposi's sarcoma and primary effusion lymphoma, while the remainder of MCD are of unknown cause. The form of MCD most closely associated with KSHV is the plasmacytic form of Castleman's disease while another pathologic form, the hyaline-vascular form, is generally negative for this virus.

MCD Symptoms
The most common 'B Symptoms' of MCD are high fevers, anemia, weight loss, loss of appetite, and low white blood cell counts, which may to be due to the overproduction of interleukin 6. Symptomatically, therefore, MCD can be difficult to diagnose and even in the case of a lymph-node biopsy a conclusive diagnosis remains problematic.

Castleman's is seen in POEMS syndrome and is implicated in 10% of cases of paraneoplastic pemphigus.

Unicentric
In the Unicentric form of the disease, surgical resection is often curative, and the prognosis is excellent.

Multicentric
There is no standard therapy for MCD at the moment.

It is important to distinguish AIDS-related Multicentric Castleman’s disease from other forms of Multicentric Castleman’s disease. Treatment for the former can be focused upon the same protocols used for treating the underlying AIDS.

Prior to 1996 MCD carried a poor prognosis of about 2 years, due to autoimmune hemolytic anemia and non-Hodgkin's lymphoma which may arise as a result of proliferation of infected cells. The timing of diagnosis, with particular attention to the difficulty of determining the cause of B symptoms without a CT scan and lymph node biopsy, may impact significantly on the prognosis and risk of death. Left untreated, MCD usually gets worse and becomes increasingly difficult and unresponsive to current treatment regimens.

Recent work with HIV-positive patients with KSHV-related MCD suggests that treatment with the antiherpesvirus drug ganciclovir or the antiCD20 B cell monoclonal antibody, rituximab, may markedly improve outcome. These drugs target and kill B cells using the CD20 marker of a patient's antibody. Since B cells are required for the production of antibodies, the body's immune response is weakened whilst on treatment and the risk of further viral or bacterial infection is increased. Due to the uncommon nature of the condition there are not many large scale research studies from which standardized approaches to therapy may be drawn, and the extant case studies of individuals or small cohorts should be read with caution. As with many diseases, the patient's age, physical state and previous medical history with respect to infections may impact on the disease progression and outcome.

Use of tocilizumab has been proposed. Other treatments for multicentric castleman disease include the following:
 * Corticosteroids
 * Chemotherapy
 * Thalidomide