Castleman disease and cancer
Castleman disease is a rare lymphatic disorder characterized by benign tumor growth, primarily affecting lymph nodes. It is classified into two main forms: localized (unicentric) and multicentric. The localized type typically remains confined to a single area and is often asymptomatic, while the multicentric type can impact multiple regions of the body and is associated with various symptoms, including fever, fatigue, and organ enlargement. The disease's etiology is not entirely understood, but overproduction of interleukin-6 and the presence of human herpesvirus 8 (HHV-8) are believed to contribute to its development, particularly in multicentric cases.
Castleman disease is more frequently diagnosed in individuals with HIV, especially those who have progressed to AIDS. While there is no established screening method, diagnosis usually involves imaging studies and elevated IL-6 levels, with confirmation through biopsy. Treatment approaches vary depending on the disease type, with localized cases often managed through surgical removal and multicentric cases treated with chemotherapy, immunotherapy, and corticosteroids. Despite its complexity, the prognosis for localized forms is generally positive, while multicentric cases present more challenges, particularly for HIV-positive patients.
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Subject Terms
Castleman disease and cancer
ALSO KNOWN AS: Angiofollicular lymph node hyperplasia, angiomatous lymphoid, Castleman tumor, giant benign lymphoma, Castleman’s disease
RELATED CONDITIONS: Angiocentric immunoproliferative lesion; lymphomatoid papulosis; polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma-proliferative disorder, skin changes (POEMS) syndrome
DEFINITION: Castleman disease is a rare lymphatic system disorder that causes benign tumor growth. Two broad forms are generally recognized: localized (or unicentric-UDC) and multicentric (MCD). MCD involves several different areas of the body. There are four microscopic subtype classificationshyaline vascular, plasma cell, mixed, and plasmablastic. The hyaline vascular subtype is predominantly localized, while plasma cell and plasmablastic subtypes may be either localized or multicentric, though they tend to be multicentric.
Risk factors:Human immunodeficiency virus (HIV) infection is the only known risk factor. Multicentric Castleman disease is much more common in HIV patients, particularly in those who have developed acquired immunodeficiency syndrome (AIDS).
Etiology and the disease process: The etiology of this disease remains unknown. Increased production of interleukin-6 (IL-6) in the lymph nodes may play a role in the development of the disease. Human herpesvirus 8 (HHV-8), or Kaposi sarcoma herpesvirus, also plays a role in the development of the multicentric type.
Incidence: Although the number of patients diagnosed annually is unknown, Castleman disease is rare. The number of cases has risen over the decades, however, as the incidence of HIV infection has increased. The National Organization for Rare Disorders estimated in 2010 that there were about thirty thousand cases in the United States. From 2016-2019, nearly 800 patients were admitted to hospitals diagnosed with Castleman disease.
Symptoms: Most patients with the hyaline-vascular type are asymptomatic. Those with the plasma cell type may have excessive sweating, fatigue, fever, skin rash, or weight loss. Those with the multicentric type may have a variety of symptoms depending on the areas affected; a common finding is an enlarged liver or spleen.
Screening and diagnosis: There is no screening method. Diagnosis typically begins after the appearance of benign lymphatic tumors on imaging studies and the presence of elevated IL-6 levels. A definitive diagnosis can be made only by removing or biopsying the tumor for histologic examination.
Treatment and therapy: Therapy is usually symptomatic. The most common treatment for localized types is surgical removal of the tumor. Radiation therapy can be used as a follow-up to surgery, particularly in cases where not all of the tumor can be removed. Corticosteroids are used to treat specific symptoms associated with the multicentric type, which is often treated with chemotherapeutic agents. Immunotherapy and antiviral medications may also be used alone or in combination with other pharmacological treatments.
Prognosis, prevention, and outcomes: The prognosis for the UCD localized types is good following complete surgical removal of the tumor. With treatment, UCD will not impact life expectancy. The prognosis is also favorable for those with MCD. Nonetheless, 75 percent of those diagnosed with MCD are still alive after five years. For patients with the more serious MCD, there is a reported three-year disease-free survival rate of 46 percent for those who are HIV-negative. For those HIV-positive, this dropped to 28 percent.
Bibliography
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Patel, Rushin et al. “Castleman Disease- Demographics, Associations, and Outcomes: An Analysis of Adult 791 Cases.” Annals of Hematology vol. 103, no.4, 2024, pp. 1255-60. https://doi.org/10.1007/s00277-023-05574-y