Castleman Disease

What Castleman disease is

Lymph nodes are filters packed with immune cells. In Castleman disease, these nodes enlarge and show a characteristic pattern under the microscope, with changes in the germinal centers and blood vessels. In multicentric disease, immune cells release large amounts of signaling proteins (cytokines), especially interleukin-6 (IL-6), which drive fever, inflammation, anemia and fluid leakage. The condition is named after Dr Benjamin Castleman, who described it in the 1950s.

Types of Castleman disease

Unicentric Castleman disease is the most common form and is often found in young adults. Multicentric forms are rarer and more serious.

Symptoms

Unicentric

• a painless, enlarged lymph node or mass, often in the chest, neck, abdomen or armpit
• pressure symptoms such as cough, breathlessness or a feeling of fullness if the mass is large
• many people have no symptoms, and the mass is found on a scan
• some have mild inflammatory symptoms that resolve after surgery

Multicentric

• fever and drenching night sweats
• weight loss and loss of appetite
• fatigue and weakness
• multiple swollen lymph nodes
• enlarged liver and spleen
• fluid buildup: swollen legs, fluid in the belly or around the lungs
• skin rashes, including cherry angiomas
• anemia, low or high platelets, kidney problems, and nerve damage in POEMS

Causes

• Unicentric: cause unclear. It may arise from a mutation in non-immune support cells of the lymph node.
• HHV-8 MCD: human herpesvirus 8 infects immune cells and makes its own version of IL-6. It mainly occurs in people with HIV or other immune suppression, and is linked to Kaposi sarcoma.
• Idiopathic MCD: cause unknown. Theories include autoimmune, autoinflammatory, cancer-like or viral mechanisms.

Castleman disease is not contagious, although HHV-8 itself can be transmitted.

Diagnosis

Castleman disease is diagnosed with a lymph node biopsy, ideally removing a whole node, interpreted by an experienced pathologist. Other tests:

• blood tests: blood count, CRP, kidney and liver function, albumin, immunoglobulins, IL-6 levels
• HIV and HHV-8 testing (HHV-8 by blood PCR and a stain on the node)
• CT or PET-CT to map how many node groups are involved
• tests to exclude other diseases that cause similar node changes, including lymphoma, lupus, rheumatoid arthritis, IgG4-related disease and infections such as EBV and tuberculosis

International criteria for idiopathic MCD combine typical biopsy findings, enlarged nodes in at least two regions, and laboratory and clinical features, after excluding other causes.

Treatment

Unicentric Castleman disease

• Complete surgical removal of the affected node or mass is curative in most cases.
• If the mass cannot be removed safely, options include radiation, rituximab, or embolization to shrink it before surgery.

HHV-8-associated multicentric

• Rituximab, an antibody targeting B cells, is the main treatment, sometimes combined with etoposide chemotherapy for severe disease.
• Antiretroviral therapy for HIV.
• Antiviral drugs against HHV-8 in some cases.

Idiopathic multicentric

• Siltuximab, which blocks IL-6, is the first-line treatment. Tocilizumab, which blocks the IL-6 receptor, is an alternative.
• Steroids to control acute flares.
• Other options for non-responders: rituximab, sirolimus, and combination chemotherapy for severe or TAFRO cases.

Outlook

Unicentric disease has an excellent outlook after removal, with normal life expectancy. Multicentric disease is more variable. Many people respond well to IL-6 blockade or rituximab and live for many years with ongoing treatment. Severe forms such as TAFRO can be life-threatening. People with MCD, especially HHV-8 MCD, have a higher risk of developing lymphoma, so long-term follow-up is important.

Frequently asked questions

Is Castleman disease a cancer?

No. Castleman disease is a disorder of the lymph nodes, not a cancer. However, it can look like lymphoma, is treated by hematologists and oncologists, and multicentric forms raise the risk of developing lymphoma later.

What is the difference between unicentric and multicentric Castleman disease?

Unicentric disease affects one group of lymph nodes, often causes few symptoms, and is usually cured by surgery. Multicentric disease affects several node groups, causes fever, sweats, weight loss and organ problems, and needs medicines such as siltuximab or rituximab.

What are the symptoms of Castleman disease?

Unicentric disease often causes only a painless lump or none at all. Multicentric disease causes fever, night sweats, weight loss, fatigue, many swollen lymph nodes, an enlarged liver and spleen, fluid buildup and anemia.

What causes Castleman disease?

The cause of unicentric and idiopathic multicentric disease is not known. HHV-8-associated multicentric Castleman disease is caused by human herpesvirus 8, mostly in people with HIV or weakened immunity.

Can Castleman disease be cured?

Unicentric Castleman disease is usually cured by removing the affected lymph node. Multicentric disease is generally controlled rather than cured, with long-term treatment such as IL-6 blockers or rituximab.