What are the pathological findings and evidence used to diagnose and treat Castleman's disease?

Pathological Findings and Evidence for Diagnosing and Treating Castleman's Disease

Castleman's disease is diagnosed through distinctive histopathological findings in lymph nodes, with treatment varying based on classification as unicentric or multicentric forms, with multicentric disease further divided into HHV-8-associated and idiopathic forms. 1

Histopathological Findings

• Castleman's disease presents with two main histological variants: hyaline vascular type and plasma cell type, with some cases showing mixed features 2
• The hyaline vascular type (most common) demonstrates:
  • Small hyalinized germinal centers surrounded by concentric layers of small lymphocytes 3
  • Vascular hyperplasia and hyalinized vessels within lymph nodes 3
  • Presence of "lollipop" follicles (follicles with radially penetrating sclerotic vessels) 2
• The plasma cell type shows:
  • Large interfollicular sheets of plasma cells 3
  • Less prominent vascular changes compared to hyaline vascular type 2
• Immunohistochemical staining typically reveals a polyclonal B-cell process in most cases 3

Diagnostic Approach

• Diagnosis requires a combination of clinical presentation, laboratory findings, and histopathological examination of affected lymph nodes 2
• Laboratory evaluation should include:
  • Complete blood count with differential (anemia is a constant finding) 1, 3
  • Inflammatory markers (C-reactive protein, erythrocyte sedimentation rate) 1
  • HIV and HHV-8 testing (critical for classification) 1
• Excisional lymph node biopsy is essential for definitive diagnosis, as fine needle aspiration cytology may be misleading 4
• Radiographic imaging helps determine disease extent (unicentric vs. multicentric) 5

Classification System

• Castleman's disease is classified into:
  • Unicentric Castleman's disease (UCD): affecting a single lymph node region 1
  • Multicentric Castleman's disease (MCD): involving multiple lymph node regions 1
    • HHV-8-associated MCD (often in HIV-positive patients) 1
    • Idiopathic MCD (HHV-8 and HIV negative) 1

Treatment Approaches

Unicentric Castleman's Disease

• Surgical excision is curative for unicentric hyaline vascular Castleman's disease 5

HHV-8-associated Multicentric Castleman's Disease

• Rituximab monotherapy is recommended as first-line treatment for HHV-8-associated MCD 1
• For severe cases, rituximab may be combined with etoposide 1
• Antiretroviral therapy should always be administered in HIV-positive patients 1

Idiopathic Multicentric Castleman's Disease

• Siltuximab (11 mg/kg intravenous infusion every 3 weeks) is FDA-approved for treatment of HIV-negative and HHV-8-negative MCD 6
• For severe inflammation or inadequate response to IL-6 blockade, triple therapy with corticosteroids, rituximab, and cyclophosphamide may be considered 7
• Monitor hematology parameters prior to each dose of siltuximab for the first 12 months and every 3 dosing cycles thereafter 6

Associated Conditions and Complications

• Castleman's disease may be associated with:
  • POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) 1, 8
  • Non-Hodgkin lymphoma (increased risk even with treatment) 1
  • Kaposi's sarcoma (particularly in HIV-positive patients) 3
  • Plasma cell dyscrasias 8
• In cases with renal complications, bortezomib-based regimens may be considered for patients with monoclonal immunoglobulin deposition disease components 7

Follow-up and Monitoring

• Clinical follow-up every 3-6 months is recommended 1
• Monitor for:
  • Disease relapse 1
  • Development of non-Hodgkin lymphoma 1
  • Progression of associated conditions like Kaposi's sarcoma 1
• Splenectomy may be considered in cases with severe refractory anemia and thrombocytopenia 1

Diagnostic Pitfalls

• Castleman's disease is a great mimic of both benign and malignant conditions, including lymphoma, metastatic adenopathy, and infectious/inflammatory diseases 5
• Accurate diagnosis requires thorough clinicopathologic correlation, as histopathologic features alone may lack specificity 2
• In patients with plasma cell neoplasia or POEMS syndrome, lymph nodes may show Castleman disease-type features, requiring additional testing to detect clonal plasma cell populations 8
• B-cell clonality analysis may help identify clonal populations in cases without morphologically identifiable monotypic plasma cells 8