Castleman's syndrome

Castleman's syndrome (Castleman Disease (CD)) is characterised by benign hyperplasia of lymph nodes:

• is an uncommon benign lymphoproliferative disorder characterized by hyper-vascular lymphoid hyperplasia (1)
  • has no sex predilection, and the age of presentation ranges from 5 years to 70 years
  • ooccurs in any area of the body where lymph nodes are found, such as mesentery, axilla, groin, lung, pelvis and the retroperitoneum
  • been reported in the tongue, palate, lymph nodes within parotid gland parenchyma and capsule
  • mediastinum is the most common site of occurrence followed by head-neck region
  • isolated Castleman's disease in the neck is rare
• can be subclassified as (2):
  • unicentric CD (UCD) involves one enlarged lymph node region
  • multicentric CD (MCD) involves multiple enlarged lymph node regions
    • can be associated with excessive cytokine production due to a plasma cell neoplasm (MCD–polyneuropathy, organomegaly, endocrinopathy, monoclonal paraprotein, skin changes) or uncontrolled human herpesvirus-8 infection (HHV-8) (HHV-8–positive MCD)
    • more than half of cases are idiopathic (1)
      • idiopathic MCD (iMCD) can be classified into three subtypes:
        • iMCD–thrombocytopenia, anasarca, fever, renal dysfunction/reticulin fibrosis, organomegaly (TAFRO)
          • hallmarks of this form are rapid onset cytokine storm with severe inflammation, anasarca, thrombocytopenia, and small volume lymphadenopathy, similar to hemophagocytic lymphohistiocytosis or sepsis
        • iMCD–idiopathic plasmacytic lymphadenopathy (IPL)
          • features include subacute or chronic lymphadenopathy, anemia of inflammation, and polyclonal hypergammaglobulinemia, often with increased IgG4 in serum and lymph node tissue;
        • iMCD-not otherwise specified (NOS)
• both UCD and MCD may exhibit a wide range of symptoms that overlap with other immune-mediated conditions

POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, Skin changes) syndrome is a rare paraneoplastic disorder that may be associated with CD (1).

Management of CD

• preferred management of unicentric CD is complete surgical excision, which is curative in approximately 95% of patients (1)
• medical treatments for CD can be considered in three categories (2):
  • immunomodulators such as glucocorticoids, cytokine inhibitors, and sirolimus
  • antilymphoma therapies such as rituximab, cytotoxic chemotherapy, and BTK inhibitors
  • antimyeloma therapies such as thalidomide and bortezomib. The first-line therapy for all subtypes of iMCD is siltuximab, an IL-6 antagonist

Reference:

1. Srivastava H, Reddy DS, Shah SN, Shah V. Castleman's disease. J Oral Maxillofac Pathol. 2020 Sep-Dec;24(3):593.
2. Chen, L.Y.C., Zhang, L. and Fajgenbaum, D.C. (2025), Expert Perspective: Diagnosis and Treatment of Castleman Disease. Arthritis Rheumatol.