Castleman disease

Castleman disease (CD), also known as angiofollicular lymph node hyperplasia or giant lymph node hyperplasia, is a rare lymphoproliferative disorder characterized by abnormal overgrowth of lymph node tissue. It is not a cancer per se but is classified among lymphoproliferative disorders. Castleman disease exists in two major clinical forms: unicentric Castleman disease (UCD), which affects a single lymph node region, and multicentric Castleman disease (MCD), which involves multiple lymph node stations and is a systemic illness. MCD is further subdivided into human herpesvirus 8 (HHV-8)-associated MCD and idiopathic multicentric Castleman disease (iMCD). The disease primarily affects the lymphatic system but can have widespread effects on multiple organ systems including the hematologic, hepatic, renal, and pulmonary systems. Unicentric Castleman disease typically presents as an enlarged lymph node mass, most commonly in the chest (mediastinum), abdomen, or neck, and may be discovered incidentally or cause compressive symptoms. It generally follows a benign course and is often curable with surgical resection. Multicentric Castleman disease presents with systemic symptoms including fever, night sweats, weight loss, fatigue, generalized lymphadenopathy, hepatosplenomegaly, fluid accumulation (ascites, pleural effusions), and laboratory abnormalities such as anemia, elevated inflammatory markers (C-reactive protein, erythrocyte sedimentation rate), hypoalbuminemia, and hypergammaglobulinemia. Severe cases of iMCD can progress to life-threatening organ failure. Treatment depends on the subtype. UCD is primarily managed with complete surgical excision, which is curative in most cases. For MCD, treatment options include the anti-interleukin-6 receptor antibody siltuximab (FDA-approved for iMCD), tocilizumab (approved in Japan), rituximab (particularly for HHV-8-associated MCD), corticosteroids, and combination chemotherapy for refractory cases. The pathogenesis of iMCD involves dysregulated interleukin-6 (IL-6) signaling and cytokine storm, though not all cases are IL-6 driven. Prognosis varies significantly between subtypes, with UCD having an excellent prognosis and MCD carrying a more guarded outlook depending on disease severity and treatment response.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Castleman disease