What Is Castleman Disease

It is an abnormal growth process of lymph nodes that causes them to enlarge in one or several areas of the body.¹ Sometimes, this disorder can present with a lymphoid mass in the chest or abdomen. No definitive overall cause is identified, but certain viral infections are linked to some of the cases.² It is important to diagnose Castleman Disease as it may mimic a blood cancer. Treatment is usually either surgical resection or systemic therapy, followed by careful monitoring.

Castleman Disease occurs mostly in the fourth to seventh decade of adults, but it can occur at any age. There are three subtypes depending on how and where it occurs in your body.  These types are unicentric, multicentric or oligo-centric.³

A definitive cause for the unicentric type is not yet recognized. The multi-centric type, in some instances, is caused by a viral infection called HHV-8.³

The disease will present as enlarged lymph nodes in various areas of the body. The unicentric type causes only one group of nodes to grow, while other multi-centric and oligo-centric types can cause growth in many groups like neck, armpits, groin, etc, and even inside your chest.

You may also get some generalized symptoms like loss of appetite, fatigue or some changes in blood and other organs due to Castleman Disease of the multi-centric type. It is important to test for Castleman Disease as sometimes it can mimic a blood cancer. It is also important to treat this disease carefully and continue to monitor and follow up after treatment since it can recur and rarely can progress into blood cancer. 

What is the background of castleman's disease?

The exact cause of Castleman Disease is not very well understood. However, the basis for the disorder seems to be a dysregulation in the immunity process that causes the immune cells, also known as lymphocytes, to increase in numbers.² It is believed that some kind of chronic inflammation or a viral infection can provide the background for this condition.

What are the types of castleman disease and symptoms?

There are mainly 3 types of Castleman Disease based on how the disease manifests in the body. The three types are unicentric, multi-centric and oligo-centric.³ Depending on the type, the symptoms that occur can vary.

As the name suggests, the unicentric type occurs in only one region of the body and is a localized disease. This can be commonly found within the central area of the chest, called mediastinum, in the back part of the abdominal cavity (retroperitoneum), or as lymph nodes elsewhere. ³ The unicentric subtype tends to be asymptomatic, or it can cause problems due to compression of adjacent structures due to enlarging lymph nodes. This can even present as pneumonia if in the chest or as abdominal pain if in the abdomen. Systemic symptoms like fever, night sweats or weight loss are rare.

Multi-centric disease can cause growth in several lymph node groups in the body. This subtype can also cause generalized symptoms that range from fever, fatigue and breathlessness to anaemia and enlargement of the spleen, etc. All these features of the multi-centric disease are said to be due to small protein molecules that manage metabolic processes in the body.⁴ These are called cytokines.

In addition, the multi-centric type is associated with other syndromes called POEMS and TAFRO. These names are abbreviations for a collection of symptoms and disease processes that occur together.³

POEMS syndrome:³

• P-polyneuropathy means disease in different nerves of the body.
• O -organomegaly, meaning enlargement of organs 
• E  -endocrinopathy, meaning disorders in the hormone system
• M- means an increase in a special protein called M
• S -skin changes

Also TAFRA syndrome:³

• T-thrombocytopaenia, meaning low platelets
• A- anasarca, which means swelling of the body due to the accumulation of fluid 
• F-fever
• R -reticulin fibrosis, which means scar-like tissue formation in organs
• O-organomegaly, meaning organ enlargement.

What are the causes and risk factors?

As mentioned before, no exact cause is known for Castleman Disease, but some factors can predispose a person for this condition. This includes conditions like viral infections caused by the virus HHV-8. This virus is reported to be capable of causing the multi-centric type of Castleman Disease.

Who gets castleman disease?

All subtypes of Castleman disease usually occur in adults in the fourth to fifth decade but can occur at any age. The unicentric type is the most common of the subtypes. It is also the one seen commonly in children. 

The multicentric subtype tends to occur in slightly older populations than the unicentric type.³

How does a doctor diagnose castleman disease?

Since the lymph nodes are the places for many disorders, including infections and blood cancers, it is very important to differentiate and diagnose Castleman Disease carefully. 

Usually, a biopsy and some additional tests mentioned here are used to diagnose Castleman Disease.

Biopsy: -To diagnose this disease, a sample of the affected lymph node is needed, and this process is called a biopsy. This sample is then looked at under the microscope. Sometimes, additional tests such as immunohistochemistry are used on the biopsy to differentiate it from other illnesses like cancers. 

Microscopically, the disease is also categorized into three variants that show some association with the three known types of unicentric, multi-centric, and oligo-centric disease.

These types include:

• A hyaline vascular variant, which tends to be the common type in unicentric disease
• Plasma cell variants tend to be more commonly seen in the HHV-8-associated multi-centric disease.
• The mixed type can occur in all three types of disease.

Imaging:  A type of scan called PET or CT scan is used to detect where the lymph nodes are located, especially in the chest or in the posterior part of the abdominal cavity called the retroperitoneum

Blood tests - When multi-centric type Castleman Disease occurs, it often occurs with systemic issues or sometimes with other syndromes, as mentioned above. These syndromes cause changes in blood and sometimes in liver and renal functions that can be detected in blood tests.

What are the treatment options?

The treatment depends on the type of Castleman Disease and the presence of symptoms.

The unicentric type is usually limited to one site and sometimes may not even need treatment right away if the patients do not have symptoms.  On the other hand, if they are symptomatic, removing the nodes surgically is often enough. If there are many nodes causing compression symptoms, resection is done to reduce the bulk of the disease.³ Sometimes, medical treatment, radiotherapy or blocking the blood supply to the region called embolization is used.

Multi-centric disease, if asymptomatic, may not need immediate treatment, but follow-up is needed often to see progression. For symptomatic patients, the treatment is based on causative factors. For example, if its a person with HHV 8 infection, treatment is likely to be anti-retroviral therapy.

Then, there are other treatment regimes like combination chemotherapy or steroids. Sometimes, even a stem cell transplant is considered for advanced disease affecting blood cells and bone marrow.

What are the outcomes of Castleman Disease?

The unicentric type is usually said to have good outcomes. Surgical resection was said to be curative until recently. However, lately, a few cases have been reported of this type converting to another cancer called Kasposi’s sarcoma or other lymphomas.⁵ Hence, long-term follow-up and monitoring is also essential for the unicentric variant. 

Multi-centric Castleman Disease is more of a systemic disease and is generally known to have a poor prognosis. One study reported a survival time of about 26 months.⁵ However, the outcome varies in individual cases and depends on the complications and associated syndromes. 

FAQs

Can castleman disease spread from person to person?

It is not an infection and, therefore, does not spread from person to person.

Summary

Castleman Disease is a type of growth disorder occurring in lymph nodes and rarely in lymphoid tissue in other parts of the body. It causes one or more nodes to enlarge due to a defect in the immunity regulation process within the nodes. The disease requires proper diagnosis as it can often be confused with some blood cancers in the lymph nodes. 

Castleman Disease can be diagnosed with a lymph node biopsy. Sometimes, additional imaging is needed, as well as blood tests. There are three main forms of the disease: unicentric, multicentric and oligo-centric. The treatment depends on these subtypes and on the presence of symptoms.

It can be treated surgically and /or by medical treatment. The unicentric type usually has a good outcome and is mostly cured with surgical resection. Multi-centric disease usually needs a wide array of treatment options such as medication, chemotherapy, radiotherapy, etc. Multicentric type may also be associated with some other syndromes. Rarely, Castleman Disease may progress to an aggressive blood cancer. Therefore, long-term monitoring is needed for all the subtypes.