What is Castleman Disease?
Castleman disease is a rare lymphoproliferative disorder characterized by non-cancerous lymph node enlargement with specific histopathological features, classified into two main forms: unicentric Castleman disease (UCD) affecting a single lymph node region, and multicentric Castleman disease (MCD) involving multiple lymph node stations. 1, 2
Classification and Subtypes
Castleman disease is divided into distinct clinical entities based on anatomic distribution and viral etiology:
Unicentric Castleman Disease (UCD): Localized disease involving a single enlarged lymph node or lymph node region, representing approximately 75% of all Castleman disease cases 2, 3
Multicentric Castleman Disease (MCD): Systemic disease with enlargement of multiple lymph node regions, accounting for approximately 25% of cases, further subdivided into:
Pathophysiology
The disease involves hyperproliferation of specific B cells that produce the cytokine interleukin-6 (IL-6), which drives the clinical manifestations 1, 6
Epidemiology
- Annual incidence in the United States is estimated at 6,500 to 7,700 cases 2
- The disease is often undiagnosed or misdiagnosed due to its rarity 1
- Can occur at any age, though specific age predilections vary by subtype 7
Clinical Presentation
Unicentric Castleman Disease
- Presents as benign, painless, slow lymph node enlargement that is generally asymptomatic 1
- Well-circumscribed mass on imaging with intense homogeneous enhancement 7
- Excellent prognosis following complete surgical resection 1
Multicentric Castleman Disease
- Progressive clinical course with systemic symptoms including fever, night sweats, and weight loss 8
- Multiple enlarged lymph nodes across different anatomic regions 2
- Associated laboratory abnormalities including anemia, elevated inflammatory markers, and hypergammaglobulinemia 4
- Potential for malignant transformation, particularly to non-Hodgkin lymphoma 4
Diagnostic Criteria
Diagnosis of idiopathic MCD requires all of the following 2:
- Characteristic histopathologic findings on lymph node biopsy showing specific microscopic changes 2
- Enlargement of multiple lymph node regions 2
- Multiple clinical and laboratory abnormalities including complete blood count with differential and inflammatory markers 4
- Exclusion of infectious, malignant, and autoimmune disorders that can mimic iMCD 2
Essential Testing
- Complete blood count with differential 4
- Inflammatory markers 4
- HHV-8 testing to distinguish between HHV-8-associated and idiopathic MCD 4
- HIV testing, as HIV-positive status is associated with HHV-8-related disease 4
Associated Conditions
Castleman disease can be associated with several secondary conditions:
- Immune complex-mediated MPGN (membranoproliferative glomerulonephritis) can occur as a secondary manifestation 9
- POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes) may be associated with Castleman disease 4
- Increased risk of developing non-Hodgkin lymphoma, particularly in MCD 4
Prognosis
Unicentric Disease
- Benign clinical course with excellent prognosis after complete surgical resection 1
- All 48 UCD patients in one retrospective series achieved cure with surgical excision 1
Multicentric Disease
- More aggressive course with potential for malignancy 1
- Five-year survival of 68% with modern therapies, particularly interferon-based treatment 4
- Rituximab treatment reduces but does not eliminate the risk of non-Hodgkin lymphoma 4
Common Pitfalls
- Misdiagnosis: The disease is frequently confused with lymphoma, infectious lymphadenopathy, or other lymphoproliferative disorders due to its rarity 1
- Incomplete workup: Failure to test for HHV-8 and HIV status can lead to inappropriate treatment selection, as siltuximab does not bind to virally-produced IL-6 6
- Aggressive UCD variants: Some cases of UCD with spindle cell proliferation may behave more aggressively than typical UCD 3