Castleman disease is a rare disorder characterized by the overgrowth of cells within the body’s lymph nodes. The condition stems from a hyperactive immune system where cells become overactivated, leading to enlarged lymph nodes and inflammation. Although it involves abnormal cell growth, Castleman disease is not a cancer, but rather a lymphoproliferative disorder. It can affect individuals of any age or gender, with diagnoses occurring most frequently between the ages of 30 and 60.
The Different Types of Castleman Disease
Castleman disease is broadly classified into two main types: Unicentric Castleman Disease (UCD) and Multicentric Castleman Disease (MCD). The distinction is based on the number of lymph node regions affected and is important for understanding the disease’s progression and treatment.
UCD is the more common form, accounting for roughly three-quarters of all cases. It is a localized disorder, meaning it affects a single lymph node or a single cluster of lymph nodes in one specific area of the body, such as the neck, chest, or abdomen. The underlying cause of UCD remains unclear to researchers.
MCD is a systemic illness that involves multiple regions of lymph nodes throughout the body and is characterized by a more significant and widespread inflammatory response. MCD is further divided into subtypes based on its cause. One major subtype is HHV-8-associated MCD, which is linked to an uncontrolled infection with human herpesvirus-8. This type is most often diagnosed in people with compromised immune systems, particularly those who are also positive for HIV.
When MCD is not caused by HHV-8, it is classified as idiopathic MCD (iMCD), meaning its cause is unknown. Researchers are exploring various potential triggers for iMCD, including other infections and genetic mutations. Differentiating between the MCD subtypes is an important step, as their treatment approaches are distinct.
Signs and Symptoms
The signs and symptoms of Castleman disease vary significantly depending on whether the condition is unicentric or multicentric. Many people with UCD do not notice any symptoms, and the condition is often discovered incidentally during medical imaging for other reasons. When symptoms do occur, they are mild and localized.
In cases of UCD, the most common sign is a single, painless lump under the skin, which is the enlarged lymph node. This lump is often found in the neck, collarbone area, or armpit. If the affected lymph node is in the chest or abdomen, it may grow large enough to press on nearby organs, causing a feeling of fullness, pressure, or pain.
Conversely, MCD presents with systemic and often more severe symptoms due to widespread inflammation. The disease can affect internal organs, leading to an enlarged spleen or liver. Common signs include:
- Fever
- Persistent fatigue
- Night sweats
- Unintentional weight loss
- Nausea and vomiting
- Swelling in the feet and ankles from fluid retention
The Diagnostic Process
Confirming a diagnosis of Castleman disease begins with a physical examination and review of the patient’s medical history. During the physical exam, a doctor will feel for enlarged lymph nodes in different parts of the body and assess any reported symptoms.
Imaging tests are then used to visualize the lymph nodes inside the body. Computed tomography (CT) scans of the neck, chest, abdomen, and pelvis are commonly performed to locate enlarged lymph nodes and determine how many regions are affected. A positron emission tomography (PET) scan can also help distinguish between UCD and MCD and assess the activity of the nodes.
Blood and urine tests provide further insight by detecting abnormalities associated with the disease. These tests can reveal signs of inflammation, anemia, or abnormal blood protein levels. For individuals with suspected MCD, blood tests are also performed to check for the presence of HHV-8 and HIV, which helps to classify the specific subtype.
The definitive step in diagnosing Castleman disease is a lymph node biopsy. A surgeon removes either a part of or the entire enlarged lymph node for examination by a pathologist. Under a microscope, the pathologist looks for characteristic features of the disease, which confirms the diagnosis and is necessary to rule out other conditions with similar symptoms, like lymphoma.
Treatment Approaches
Treatment for Castleman disease is tailored to the specific type, as the approaches for UCD and MCD differ. For UCD, the standard treatment is the complete surgical removal of the affected lymph node. In most cases, this procedure is curative, and patients are free of the disease after removal.
If the enlarged lymph node in UCD is in a location that makes surgery difficult or risky, other options may be considered. Radiation therapy can be used to shrink the node and is an alternative for patients who are not candidates for surgery. In some instances, immunotherapy drugs may be administered before surgery to reduce the size of the lymph node, making it easier to remove.
Because MCD affects multiple lymph node regions, surgery is not a practical solution. Instead, treatment relies on systemic medications to control the overactive immune system and inflammation. A primary treatment for iMCD is immunotherapy targeting the interleukin-6 (IL-6) pathway. Drugs like siltuximab block the action of IL-6, a protein that drives inflammation in the disease.
For HHV-8-associated MCD, treatment often includes antiviral therapies to manage the underlying viral infection, alongside other medications. The drug rituximab, which targets a type of immune cell called B cells, is frequently used and is effective for this subtype. In more severe cases of either MCD subtype, corticosteroids may be used to reduce inflammation, and chemotherapy can be employed to suppress the rapid growth of lymphatic cells.
Outlook and Prognosis
The long-term outlook for individuals with Castleman disease largely depends on the type they are diagnosed with. The prognosis for UCD is excellent. Since the disease is localized, surgical removal of the affected lymph node is often a complete cure, and the majority of people with UCD go on to live a normal life without recurrence.
For those with MCD, the condition is more serious and is considered a chronic illness that requires ongoing management. While MCD is not cured in the same way as UCD, modern treatments have significantly improved the prognosis and quality of life for many patients. The five-year overall survival rate for MCD has historically been around 65-75%, but this is expected to improve as newer, targeted therapies become more widely used.