Castleman Disease

Castleman disease (CD) encompasses a group of rare lymphoproliferative conditions with distinct clinical and pathological features. It is broadly divided into unicentric CD (UCD), involving a solitary lymph node region, and multicentric CD (MCD), with multinodal involvement and systemic manifestations. MCD is further subtyped based on etiology into HHV-8–associated, idiopathic (iMCD), and POEMS-related forms. While interleukin-6 (IL-6) has been known for a long time to play a key role in the disease, new research shows that other cytokines, like CXCL13, and certain cell pathways, such as PI3K/Akt/mTOR, are also involved, especially in cases that don’t respond to IL-6 treatment. Excisional lymph node biopsy and thorough clinical evaluation are necessary for accurate diagnosis and to rule out mimics such as lymphomas and autoimmune diseases. Therapeutic decisions are based on the subtype and disease severity: UCD typically requires only surgery, whereas MCD requires systemic treatment, such as targeted biologic agents or cytotoxic chemotherapy. This chapter outlines the evolving framework for diagnosis, classification, and treatment of Castleman disease, highlighting recent advances in understanding its pathogenesis.