Unicentric Castleman disease

by Jason Wasserman MD PhD FRCPC and David Li MD
June 2, 2025

Unicentric Castleman disease (UCD) is a rare, non-cancerous condition that affects lymph nodes. Lymph nodes are small structures found throughout the body that help fight infection. In UCD, only a single lymph node or a group of lymph nodes in a specific area is involved. UCD typically has benign features, meaning it is not cancerous and usually does not spread to other parts of the body.

What are the symptoms of unicentric Castleman disease?

Many people with unicentric Castleman disease do not experience any noticeable symptoms. Often, an enlarged lymph node is discovered accidentally during a physical examination or imaging tests performed for unrelated reasons. When symptoms do occur, they are typically caused by the enlarged lymph node pressing against nearby tissues or organs.

These symptoms can include:

• Pain or discomfort due to pressure.

• A visible lump or swelling, especially in the neck, chest, or abdomen.

• Difficulty breathing if the affected lymph node is near the lungs or airways.

A small number of patients with UCD may experience inflammatory symptoms similar to those seen in multicentric Castleman disease, such as fatigue, fever, night sweats, or weight loss. Very rarely, patients may also develop autoimmune or other inflammatory conditions.

What causes unicentric Castleman disease?

The exact cause of unicentric Castleman disease is currently unknown. However, researchers suspect it results from abnormal growth of certain immune-related cells, called follicular dendritic cells, within the affected lymph node. Genetic changes have been found in some cases, suggesting that these cells may grow abnormally due to specific gene mutations. Unlike multicentric Castleman disease, UCD is not associated with infection by viruses such as human herpesvirus-8 (HHV8).

How is unicentric Castleman disease diagnosed?

The diagnosis of unicentric Castleman disease typically begins when a doctor discovers a single enlarged lymph node during a physical examination or through imaging tests such as CT scans or MRI. To confirm the diagnosis, a biopsy is performed, where a sample of tissue is taken from the affected lymph node and examined under a microscope by a pathologist. Additional laboratory tests, including blood tests, may help rule out other similar conditions and assess for inflammation or autoimmune disorders.

What other tests may be performed to confirm the diagnosis?

Pathologists often perform special laboratory tests on the biopsy tissue, including immunohistochemistry (IHC), to help confirm the diagnosis of UCD and distinguish it from other diseases. These tests look for specific proteins expressed by different types of immune cells. For example, follicular dendritic cells usually express markers like CD21 and CD35. Tests for viruses such as HHV8 and Epstein-Barr virus (EBV) are typically negative in UCD.

What does unicentric Castleman disease look like under the microscope?

Under the microscope, lymph nodes affected by UCD show disrupted or altered organization compared to normal lymph nodes. Normally, lymph nodes contain round clusters of immune cells called follicles and areas between these follicles called interfollicular areas. In UCD, these structures become distorted or unusual-looking.

Hyaline-vascular subtype (HV-UCD)

In the most common subtype, hyaline-vascular unicentric Castleman disease, the lymph node contains many enlarged follicles. The center of these follicles (germinal centers) has fewer immune cells than usual and appears filled with specialized cells called follicular dendritic cells (FDCs). Blood vessels entering the follicles become thickened and scarred (hyalinized), creating a distinctive appearance sometimes described as “lollipop lesions.” Around these germinal centers, layers of immune cells form concentric rings resembling an onion-skin pattern. Occasionally, two or more smaller germinal centers are seen within a single follicle, which pathologists call twinning. Between the follicles, areas are filled mostly with small immune cells and fibrous (scar-like) tissue, and the normal channels (sinuses) become compressed or blocked.

Mixed/plasmacytic subtype

In the less common mixed/plasmacytic subtype, lymph nodes look somewhat more like normal lymph nodes. The follicles vary significantly in size and appearance, some appearing active and others smaller and less active. The spaces between follicles (interfollicular areas) contain large numbers of plasma cells, which are immune cells responsible for producing antibodies. These plasma cells often form dense groups or sheets, accompanied by prominent blood vessels.

What is the prognosis for unicentric Castleman disease?

Unicentric Castleman disease typically has an excellent prognosis. Surgical removal of the affected lymph node usually cures the condition, and recurrence is very rare. If the lymph node cannot be safely removed due to its location or size, alternative treatments such as radiation therapy or medication might be used. Patients with the mixed/plasmacytic subtype or those who experience inflammatory symptoms might require treatments aimed at controlling inflammation, such as medications that block specific inflammatory substances like interleukin-6 (IL-6). Overall, most people with unicentric Castleman disease live healthy, normal lives after appropriate treatment.

Rarely, patients with UCD develop associated complications, such as autoimmune conditions, certain types of lymphomas, or other disorders, which may affect the prognosis and require additional medical attention.

Questions for your doctor

• Which subtype of unicentric Castleman disease do I have?

• Has my lymph node been completely removed, or is additional treatment needed?

• Should I have regular follow-up visits or imaging studies?

• What symptoms should I watch for that might indicate recurrence?

• Are there specific medications I should take or avoid?

• Can unicentric Castleman disease cause other health issues in the future?

• Do I need any further tests to rule out associated conditions or complications?

• If surgery isn’t an option, what other treatments are available?

• Is my family at risk for developing Castleman disease?

• What resources or support groups are available to me?