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It was first described by Benjamin Castelman, an American pathologist, and his colleagues in 1956. It is also referred to as vascular-follicular lymph node hyperplasia, giant lymph node hyperplasia, benign giant lymphoma or lymph node hamartoma.
Castleman’s disease is classified as a rare disease. It usually has a mild, non-cancerous form. The disease is slightly more common in women (56% of cases). Tumor lesions can develop anywhere in the lymphatic system. In 76,6 percent patients occur in the lymph nodes, and in 23,4%. take the extra-nodal form.
The causes of the disease have not been fully understood. The most frequently repeated hypotheses include immunological or infectious. Researchers believe Ebstein-Barr 68, HHV-8 (Kaposi sarcoma-associated virus), Toxoplasma gondi and tuberculosis viruses may be pathogens contributing to the development of the disease.
Tumors occurring in the course of Castelman disease are often referred to as hamartomatic lesions. A hamartoma is a non-cancerous tumor that develops as a result of developmental disorders. It is made of mature tissues that occur naturally in an organ. However, they are chaotically distributed throughout the tumor and often appear in distorted proportions. Hamartomas can develop in any organ.
When considering the causes of Castelman disease, scientists emphasize that the key to its development may be the abnormal production of interleukin 6, which is a factor in the growth of B lymphocytes and provokes proliferation (rapid development, extensive proliferation) and differentiation into plasma cells.
Disease forms
There are usually two clinical forms of Castelman’s disease – localized and multifocal. Histologically, the vascular-vitreous and plasma-cellular forms are distinguished. They differ in symptoms and response to treatment.
Localized character usually occurs in young people. It affects a single lymph node or a group of nodes. This is called Castleman’s tumor. The lesions most often appear in the mediastinum, lung cavities, in the neck or armpit. There have also been reports of tumors in the abdominal cavity, retroperitoneal space, pelvis, salivary glands, subcutaneous tissue and skeletal muscle. The symptom of the disease is a soft tissue, well-defined nodular lesion or mediastinal dilatation, which may be accompanied by pleural effusion. Large tumors can put pressure on the lungs, which will manifest as impaired ventilation of the lungs, coughing, infections and chest pain. About 80 percent. patients with a localized form of Castelman’s disease, histologically diagnosed with the vascular-vitreous form, and in 20% plasma-cell form. The localized vitreous form is usually mild. Surgical removal of the tumor is aimed at diagnosis and treatment. The five-year survival after surgery is 94-100%. If the localized form of the disease is classified as a plasma-cell type, its course and prognosis are worse.
Multifocal form it occurs in older people, usually around the age of 58. Then also multiple lymph nodes or their packages are occupied. The disease is aggressive. Symptoms of progressive disease may include fever, night sweats, weakness and weight loss, hepatosplenomegaly, peripheral lymphadenopathy, abdominal swelling, pleural effusion, as well as anemia, increased ESR, hypoalbuminemia and hypergammaglobulinemia. Multifocal Castleman’s disease can occur together with lymphoma, Kaposi’s sarcoma, amyloidosis, myasthenia, pemphigus and POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin lesions). The most common causes of death in this form of the disease are infections, followed by malignancies such as Kaposi’s sarcoma, malignant lymphoma, and epithelial neoplasia. Histologically, in the multifocal form, the plasma-cell type predominates. The lesions located in the mediastinum are visible on the chest X-ray. Other tests that are performed in the diagnosis process are: ultrasound and computed tomography. In some patients, arteriography is also performed. Tumor biopsies are extremely rare as they have a high risk of bleeding.
Surgical removal of the tumor is the treatment of choice in monofocal forms. Even when it is not possible to completely remove the tumor, excision of part of it is beneficial for the patient. Usually the tumor does not grow back. Sometimes radiation therapy is given to reduce the mass of the tumor. If the disease is multifocal, there is no specific treatment. This form of the disease is characterized by a high, about 50%, mortality and the average survival time of about 26 months.
Treatment progress
We already know that in the case of localized disease, surgical removal of the tumor is the treatment of choice, which usually solves most of the patient’s health problems. If the tumor is located in an easily accessible place, e.g. under the armpit, in the neck area, simplified treatment procedures can be applied without the need for hospitalization. Often, such meetings are performed as part of one-day procedures. If removal of the tumor is not possible due to the location of the lymph node, modern medicine is supported by drugs called monoclonal antibodies or radiation therapy, which also destroys the diseased tissue.
The multifocal form of Castelman’s disease often requires systemic treatment. Surgical treatment does not make sense because it is impossible to remove so many lymph nodes.
In such situations, monoclonal antibodies are also used to neutralize or block the activity of interleukin 6 (IL-6). Another monoclonal antibody is rituximab, a drug that targets another type of cell that causes Castelman disease. In some people, the use of such therapy leads to complete remission of the disease. However, it is important to know that the treatment is associated with the risk of side effects such as fever, headache, fatigue, rash and nausea.
In some patients, administration of corticosteroids, which have an anti-inflammatory effect, has been proven. The administration of steroids is usually combined with other therapies. However, long-term use of steroids may reduce resistance to infections, increase blood pressure, and contribute to weight gain and bone weakness (risk of osteopenia and osteoporosis).
The atypical course of the multifocal form of Castelman’s disease and the different individual responses of patients force doctors to seek new therapeutic solutions. In some patients, the use of a combination of anticancer drugs, i.e. chemotherapy, which, although sometimes effective, is also associated with many side effects, e.g. hair loss, loss of appetite, severe nausea or vomiting, and reduced resistance to infections, is successful.
Sometimes patients are also given antiviral drugs, such as ganciclovir, which inhibit the activity of the HHV-8 virus. Another method of therapy used is the administration of immunological modulators, i.e. drugs that regulate the functioning of the immune system. Patients most often received interferon alpha, which not only acts on the immune system, but also has an antiviral effect. Unfortunately, the symptoms of the disease reappear after the treatment is discontinued.
Scientists are constantly looking for effective treatments for Castelman’s disease. As it is a rare disease, it is not easy to obtain financial resources for clinical trials of new drugs and new therapies.
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