Castleman's Disease

Introduction
Castleman’s disease is a rare lympho-proliferative disorder. It is defined as localized hyperplasia of lymphoid follicles with and without a germinal center formation and marked capillary proliferation with endothelial hyperplasia. It is also referred as the lymphoma impostor.

Castleman disease involves an overgrowth (proliferation) of cells in lymphatic system, the disease-fighting network of our body. Also known as giant lymph node hyperplasia and angiofollicular lymph node hyperplasia, Castleman disease can occur in a localized (unicentric) or widespread (multicentric) form.

Treatment and outlook depend on the type of Castleman disease. The localized type is effectively treated with surgery and affects only a single gland (lymph node) in your lymphatic system. This is known as the Unicentric Castleman disease. On the other hand, multicentric Castleman disease affects multiple lymph nodes and lymphatic tissues. It can be extremely fatal as it can weaken immune system severely. Multicentric Castleman disease is also associated with other cell-proliferation disorders such as cancer of the lymphatic system (lymphoma), Kaposi’s sarcoma and POEMS syndrome.

Symptoms
Many people with unicentric Castleman disease do not exhibit noticeable signs or symptoms. The diseased lymph node is mostly situated in chest, neck or abdomen. However, a feeling of fullness or pressure in chest or abdominal region can cause difficulty breathing or eating. An enlarged lump under the skin in neck, groin or armpit is found. Unintended weight loss associated with fever, night sweats and weakness are observed.

Patients of multicentric Castleman disease experience fever, fatigues and weakness along with loss in appetite and weight. Enlarged lymph nodes, usually around the neck, collarbone, underarm and groin areas are seen. Nerve damage leading to numbness in hands and feet along with skin rash has been observed.

Causes
Cause of Castleman disease is not clearly defined. However, multicentric Castleman disease is said to be caused due to an infection by a virus called human herpes virus 8 (HHV-8).

This virus is linked to the development of Kaposi’s sarcoma, a cancerous tumor of the blood vessel walls, which is likely to be a complication of HIV/AIDS. Studies have found that HHV-8 is present in HIV-positive people who have Castleman disease and in 40 to 50 percent of HIV-negative people with Castleman disease. The immune system cells produce a protein called interleukin-6 (IL-6) that contributes to the overgrowth of lymphatic cells.

Diagnosis
When unicentric or multicentric Castleman disease is suspected, the healthcare specialist does a thorough physical examination of lymph nodes, to find their size and consistency.

Further, Blood and urine tests are done to delineate other infections or diseases. These tests can also reveal anemia and abnormalities in blood proteins specific to Castleman disease. Imaging tests such as CT scan or MRI are done to detect enlarged lymph nodes on liver or spleen by checking the neck, chest, abdomen and pelvis. Positron emission tomography (PET) scans also may be used to diagnose Castleman disease to ascertain the efficacy of the treatment. Lymph node biopsy is performed to differentiate Castleman disease from other types of lymphatic tissue disorders, such as lymphoma. A tissue sample from an enlarged lymph node is removed and examined in the laboratory.

Treatment
Treatment depends on the type of Castleman disease a patient has. Unicentric Castleman disease is found to be cured by surgical removal of the diseased lymph node. If the lymph node is found to be in chest or abdomen, major surgery may be required.

However, if surgical removal is not feasible, medication may be used to shrink the lymph node. Radiation therapy also may be an effective way to destroy the affected tissue. Follow-up exams are necessary to check for relapse.

Since there is higher number of lymph nodes in multicentric Castleman disease surgery is not a feasible option. However, enlarged spleen can be removed surgically to alleviate the symptoms.

Treatment usually involves medications and other therapies to control cell overgrowth. Specific treatment depends on the extent of disease and if one has HIV or HHV-8 infection or both.

Medications include monoclonal antibodies that block the action of the IL-6 protein contributing to cell overgrowth. The healthcare specialist may prescribe siltuximab (Sylvant) for initial treatment with a monoclonal antibody, if patient’s organ is not damaged due to HIV or HHV-8 infection.

Chemotherapy is recommended to slow overgrowth of lymphatic cells. Corticosteroids are recommended to control inflammation. Antiviral drugs help to block the activity of HHV-8 or HIV. Thalidomide (Thalomid) is used in blocking the action of the IL-6 protein. Thalidomide is an immune-system modulator shown to be effective at inducing remission in Castleman disease.

References
1. Castleman B, Iverson L, Menendez VP. Localized mediastinal lymphnode hyperplasia resembling thymoma. Cancer 1956; 9:822.

2. Chronowski GM, Ha CS, Wilder RB, et al. Treatment of unicentric and multicentric Castleman disease and the role of radiotherapy. Cancer 2001; 92:670.

3. Herrada J, Cabanillas F, Rice L, et al. The clinical behavior of localized and multicentric Castleman disease. Ann Intern Med 1998; 128:657.

4. Oksenhendler E, Duarte M, Soulier J, et al. Multicentric Castleman’s disease in HIV infection: a clinical and pathological study of 20 patients. AIDS 1996; 10:61.

5. van Rhee F, Wong RS, Munshi N, et al. Siltuximab for multicentric Castleman’s disease: a randomised, double-blind, placebo-controlled trial. Lancet Oncol 2014; 15:966.

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