We have found the information in these two articles reputable and helpful in answering some of our questions and/or just explaining Castleman Disease. The articles are a bit long but do a good job explaining about the disease. The first one is from the American Cancer Society. The second article is from the International Castleman Disease Organization and is a bit more technical. Hope you find these articles as informative as we have.

Article One from the American Cancer Society: "Castleman disease (CD) is a disease of lymph nodes and related tissues. It was first described by Dr. Benjamin Castleman in Boston in 1956. CD is also known as giant lymph node hyperplasia and angiofollicular lymph node hyperplasia. Although not officially a cancer, this disease can act very much like lymphoma (cancer of lymph nodes). In fact, many people with this disease eventually develop lymphomas. This is why it is included in the American Cancer Society’s cancer information database. Instead of being called a cancer, CD is often called a lymphoproliferative disorder. This means there is an abnormal overgrowth of cells of the lymph system that is similar in many ways to lymphomas. Like lymphoma, CD is frequently treated with chemotherapy or radiation therapy.

Lymphoid tissue, also known as lymphatic tissue, is the main part of the immune system. It is formed by different types of cells that work together to resist infections. Lymphoid tissue also has a role in the body's resistance against some forms of cancer. The main cell of lymphoid tissue is the lymphocyte. There are 2 types of lymphocytes: B cells and T cells.

Lymphoid tissue is found in many places throughout the body, including:

• Lymph nodes (bean-sized collections of immune system cells found clustered in the groin and underarm areas, on the sides of the neck, inside the chest, and scattered widely though the body including the abdomen)
• Thymus gland
• Spleen
• Tonsils and adenoids
• Bone marrow

Types of Castleman disease:

CD is separated into 2 groups: localized/unicentric and multicentric/systemic. They affect people very differently.

Localized Castleman disease:

Localized or unicentric CD only affects a single set of lymph nodes. It is not widespread. The lymph nodes in the chest and abdomen are affected most often. CD causes these lymph nodes to enlarge. These abnormally large lymph nodes may press on other organs and tissues inside the chest or abdomen. If they are in the abdomen, the person might feel pain or pressure in that area. Enlarged lymph nodes in the chest can press on the windpipe (trachea) or smaller breathing tubes (bronchi) causing breathing problems. Sometimes the enlarged lymph nodes are in places such as the neck, groin, or underarms and can be felt easily. People with localized CD disease are usually cured when the lymph node is removed with surgery.

Microscopic subtypes of Castleman disease:

Castleman disease can also be classified as either a hyaline vascular type or a plasma cell type based on how the lymph node tissue appears under a microscope (these are called microscopic subtypes). Less often, a combination of both types may occur. The hyaline vascular type is more common and tends to be localized, while the plasma cell type tends to be multicentric, but exceptions to this rule often occur. In choosing treatments, doctors feel that the microscopic type is less important than whether the disease is localized or multicentric.

We don't know how many people are diagnosed with Castleman disease (CD) each year. The National Cancer Institute has a program that keeps track of how many people have each type of cancer. Because CD is not a cancer, it is not included in these records. We do know that CD disease is very rare in healthy people. In fact, 2 of the leading cancer centers in the United States, MD Anderson and Memorial Sloan-Kettering, each see about 2 patients a year.

A risk factor is anything that might change a person's chance of getting a disease. But risk factors don't tell us everything. Having a risk factor, or even several, does not mean that you will get the disease. Having no risk factors doesn't mean you won't get the disease.

Most patients with Castleman disease (CD) have no known risk factors. In general, most people with localized CD disease feel well otherwise.

No one has discovered the cause of this disease, but many doctors suspect a virus is involved.

Doctors suspect that problems with the way a patients immune system is working may contribute to the development of CD. Many people with CD have abnormally high blood levels of certain substances produced by immune system cells.

Some scientists believe that CD occurs when there is too much of a protein called interleukin-6 (IL-6). IL-6 is a protein the body makes to help regulate immune function. Too much IL-6 seems to cause lymphocytes to reproduce excessively.

Treatment of localized (unicentric) Castleman disease:

Surgery is the recommended treatment for people with localized Castleman disease (CD). Removing the abnormal lymph node(s) appears to cure the disease. Symptoms such as fever and fatigue that are caused by the CD go away when the lymph node is removed. Relapses are rare. Radiation can also cure localized disease.

Some patients with localized CD develop secondary amyloidosis, a condition in which abnormal proteins build up in the kidneys, skin, and some other organs. This protein build-up stops once the lymph node affected by CD is removed.

The outlook for localized CD is very good if the affected lymph node can be removed with surgery. But sometimes the surgeon cannot safely remove all the disease. This doesn't necessarily mean it will come back. Even partial removal may help and the disease may not grow back.

Frequent follow-up exams are very important for several years after the treatment for Castleman disease (CD) is finished. The doctors will continue to watch you for signs of recurrent disease."

Article Two from the International Castleman Disease Organization: "Castleman disease is a benign disorder first described by Dr. Benjamin Castleman in 1956. Castleman disease is also referred to as angiofollicular hyperplasia, and is non-clonal disease of the lymphnodes. As the name angiofollicular hyperplasia (1) implies there is a follicular hyperplasia of lymph nodes with abnormally increased interfollicular vascularity. Castleman disease can be classified as a) unicentric vs. multicentric, based on clinical and radiological findings, b) hyaline vascular vs. plasmacytic vs. mixed cellularity variety based on histopathology. 

Unicentric Castleman Disease is usually a slow growing solitary mass typically located in the mediastinium or mesenteries. There are no constitutional symptoms and no elevation of acute phase reactants (Interleukin 6, ESR and CRP).  Symptoms if present are due to a mass effect of bulky lymphadenopathy. In 90-95% cases surgical resection is curative and usually there is no progression to lymphoma or association with other tumors. The prognosis is excellent with a 5 year survival of close to 100%.

The histopathology of hyaline vascular Castleman disease shows that the lymphnode germinal centers are poorly formed with dysplastic/ atrophic CD21+ follicular dendritic cell networks surrounded by an expanded mantle zone consisting of rims of small CD20+ lymphocytes arranged in an onion skin manner.  There is increased interfollicular vascularity with capillary proliferation and endothelial hyperplasia.

Classically it is thought that Unicentric Castleman disease is usually of the hyaline vascular variety and multicentric disease of the plasmacytic type or mixed cellularity variety. These relationships are based on the analysis of the small numbers of patients since Castleman disease is rare. Review of 37 patients with Castleman disease treated at UAMS, which is the largest single institution experience in the world with Castleman Disease. We found that patients with Unicentric Castleman disease indeed have as pathology the hyaline vascular variety. However, the histopathology of multicentric disease can be evenly divided between hyaline vascular variety on one hand and plasmacytic type and mixed cellularity variety on the other hand. Mixed cellularity clinically behaves more like plasmacytic type rather than hyaline vascular disease.

Surgical excision is the preferred treatment in most cases of unicentric Castleman Disease and adjuvant therapy e.g. steroids and/or rituxan before surgery is very useful to shrink bulky or inoperable disease. In some cases, radiotherapy has proven effective.

In most cases of the hyaline-vascular type of Castleman Disease, individuals exhibit no symptoms of this type of the disorder (asymptomatic) or may develop a non-cancerous (benign) growth in the lymph tissue; most frequently in the chest. Symptoms with this type are usually secondary to the size and location of the growth.

The hyaline vascular sub-type accounts for 90% of cases of Castleman disease and patients are generally asymptomatic (58% to 97% of patients are asymptomatic). Most patients come to clinical attention when a solitary middle or posterior mediastinal mass (adenopathy) is detected incidentally on chest radiographs. In order of frequency, the intrathoracic sites involved include the anterior mediastinum, particularly right paratracheal, hilar nodes, and the posterior mediastinum. About 70% of affected patients are less than 30 years old, and males are affected more than females. Symptomatic patients may complain of dry cough, dyspnea, or recurrent infection due to airway compression. The treatment is surgical with a low recurrence rate if the resection is subtotal. Rare cases have been complicated by the development of vascular neoplasms that resemble Kaposi's sarcoma, or Hodgkin's lymphoma .

The exact cause of Castleman Disease is not known. Some researchers speculate that increased production of interleukin-6 (IL-6) may be involved in the development of Castleman Disease. IL-6 is a substance produced by structures within the lymph nodes.

The treatment of Castleman Disease is directed toward the specific symptoms that are apparent in each individual. Specific therapies for the treatment of this disorder are symptomatic and supportive. Surgical removal (excision) of the growth is the preferred treatment in most cases of localized Castleman Disease. In some cases, ionizing radiation (radiotherapy) has proven effective."