Disease Overview

Castleman’s disease (CD) is a rare, nonclonal lymphoproliferative disorder that affects lymph nodes of any part of the body, imitating benign and malignant masts. Areas most commonly affected are the neck, chest, abdomen, and pelvis. CD can be classified into subtypes based on clinical and histological presentation. Subtypes include hyaline vascular type (HV-CD), plasma cell type, mixed type, and human herpesvirus (HHV)-8 associated CD. The hyaline-vascular variant is more common than the plasma-cell type. Clinically, CD presents as more unicentric (localized or unifocal) than multicentric (generalized or multifocal). Patients with multicentric castleman’s disease are at higher risk of life-threatening infection or organ failure compared to those with unicentric CD. Castleman’s disease is life threatening and can be fatal if left untreated. It develops primarily in patients around 30 years old and affects men and women equally. 

Diagnosis

Diagnosing castleman’s disease is challenging because its clinical presentation overlaps with other causes of lymphadenopathy. A collaborative effort between clinical and laboratory teams is crucial for accurate diagnosis, requiring thorough exclusion of other causes through biopsies, serological and histological studies, and clinical correlation. 

Diagnosis of CD hinges on meeting major criteria and at least two minor criteria. Major criteria include histopathologic screening of lymph nodes to assess involvement (either single or multimodal) and evaluating lymph node size and characteristic features. Minor criteria include clinical presentation of symptoms like fever, weight loss, night sweats, fatigue, and specific laboratory abnormalities such as elevated CRP/ESR, anemia, and abnormal immunoglobulin levels.

Presence of IL-6 serves as a significant biomarker contributing to the disease’s pathogenesis. Although other markers like sIL2R, VEGF, and specific immunoglobulins are supportive to the diagnosis, they are not specific markers to use alone for a diagnosis. In addition, serological testing for HIV and HHV-8, along with HHV-8 DNA PCR from peripheral blood, helps identify potential associations with castleman’s disease.

Staging of the disease involves comprehensive evaluations like serum protein electrophoresis, bone marrow examination, CT scans (chest, abdomen, pelvis), radiographic skeletal surveys, and gallium scans to assess disease extent and distinguish between localized and multicentric forms.

Disease Management and Treatment

Castleman’s disease is rare and treatment options are limited. For unicentric castleman’s disease, surgical removal of the localized lesion is the preferred treatment. Patients usually improve once the lymph node is surgically removed. Patients with multicentric castleman’s disease have several treatment options, including surgery, chemotherapy with or without corticosteroids, and autologous stem cell transplantation (ASCT), each with varying success rates. Targeting CD20 and IL-6 pathways, as well as suppressing HHV-8 replication, has shown promising outcomes.

Monoclonal antibodies like Tocilizumab and Siltuximab, which block IL-6 signaling, are highly effective as first-line therapies, especially for symptomatic patients not infected with HIV or HHV-8. Antiviral drugs such as ganciclovir, foscarnet, and cidofovir are effective against HHV-8. Newer immunomodulatory agents like rituximab, thalidomide, bortezomib, anakinra, and interferon-alpha have also shown promise with minimal side effects.

Chemotherapy and immunomodulatory drugs are reserved for relapses, although it’s important to note that not all castleman’s disease cases respond to treatment and achieve remission.