The goal of the Center for Castleman Disease at the Myeloma Institute is to identify novel targeted therapies that will improve patient outcomes. To achieve these goals, we are seeking a better understanding of Castleman disease by collecting long-term follow-up data from all of our patients and conducting research into the details of the development of this complex disease.
The Myeloma Institute has seen more than 140 patients with Castleman disease, which is more than any other single institution in the world. Through generous donor support, a laboratory lab focused on advancing Castleman disease research was created. The Gregory R. Pacheco Lab for Castleman Disease Research was formally dedicated on April 23, 2009.
Also referred to as angiofollicular hyperplasia, Castleman disease is a disease of the lymph nodes. This rare, benign disorder was first described in 1954 by Dr. Benjamin Castleman, who was a pathologist at the Massachusetts General Hospital in Boston. Castleman disease results from lymphatic cells that grow out of control, which is similar to lymphomas (cancers that start in lymphatic tissues). Although Castleman disease is not considered a cancer, it can develop into lymphoma. Approximately 200 new cases are diagnosed each year in the U.S.
Castleman disease has three different classifications, and all three must be considered when determining a patient’s prognosis and treatment course.
Castleman disease can be classified as:
Unicentric Castleman Disease is usually marked by a single slow-growing mass, typically located in the mediastinum (the area between the lungs) or mesenteries (membranes that surround and support the intestines). Many people with unicentric Castleman Disease notice no symptoms at all. When unicentric Castleman Disease does cause symptoms, they are usually due to the enlarged lymph node on vital structures, such as the lungs, heart.
Symptoms of unicentric Castleman Disease may include:
Unicentric Castleman Disease has an excellent prognosis: the disease usually does not progress to lymphoma, and surgically removing the tumor cures 90–95% of cases.
Multicentric Castleman Disease usually includes widespread chronic swelling of the lymph nodes, and some cases also have enlargement of the liver and spleen. Overproduction of interleukin 6 (IL6) results in many symptoms typical of multicentric Castleman Disease, which can include severe fatigue, night sweats, recurrent fever, and weight loss. Often, patients have peripheral edema, anemia, and hypoalbuminemia, and approximately 20% of patients have peripheral neuropathy (pain, numbness, or tingling in the hands, arms, legs, and feet). Multicentric Castleman disease is more aggressive than unicentric Castleman Disease and can progress to non-Hodgkin’s lymphoma (a cancer that starts in cells of the immune system). Multicentric Castleman Disease often requires systemic therapy.
People with multicentric Castleman Disease may develop some or all of these signs and symptoms:
Based on characteristic tissues changes that are identified in the diseased tissues, Castleman Disease is classified as hyaline vascular, plasmacytic or mixed cellularity. The mixed cellularity subtype has features of both hyaline vascular and plasmacytic forms, but it clinically behaves more like plasmacytic than hyaline vascular disease. A review of 37 patients with Castleman Disease treated at the Myeloma Institute showed that patients with unicentric Castleman disease most often exhibited hyaline vascular pathology. However, the histopathology of multicentric disease was evenly divided between hyaline vascular, plasmacytic, and mixed cellularity subtypes.
HIV status is important as HIV-positive patients with multicentric Castleman Disease have a less favorable clinical course than those who are HIV-negative. These HIV-positive patients more frequently have plasmacytic disease, and/or have Kaposi’s sarcoma, and progress to plasmablastic non-Hodgkin’s lymphoma.
Diagnosis of Castleman Disease is based on a thorough clinical evaluation that includes a detailed patient history, laboratory studies, histopathological analysis of affected lymph node(s) (biopsy), and imaging studies that use a variety of techniques (such as CT, MRI, and PET scans). PET scanning can be used to improve staging and detect tumors, as well as to determine biopsy location, identify disease stage, diagnose cancer recurrence, and discern malignant from benign conditions.
In most cases of unicentric Castleman Disease, the preferred treatment is surgical removal of the mass. Adjuvant therapy, such as steroids and/or rituximab before surgery, is very useful to shrink a bulky or inoperable tumor. For multicentric Castleman’s Disease, a number of therapies have been used: intravenous immunoglobulin, anti-herpes drugs (such as acyclovir), (val)ganciclovir for HIV-positive disease, combination chemotherapy, and even autologous stem cell transplantation. Surgery may be useful in multicentric disease for reducing the size and extent of tumors. Other therapies include the use of thalidomide and anti-IL6 monoclonal antibody therapy. Anti-IL6 therapy can be effective and result in long-lasting remissions. Recently, in a clinical trial at the Myeloma Institute, anti-IL6 receptor antibody produced responses equal to, if not better than, those observed with IL6 antibody.
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