What laboratory tests should be ordered for a patient suspected of having Castleman disease?

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Laboratory Evaluation for Castleman Disease

For suspected Castleman disease, order interleukin-6 (IL-6), C-reactive protein (CRP), complete blood count with differential, comprehensive metabolic panel, erythrocyte sedimentation rate (ESR), serum protein electrophoresis with quantitative immunoglobulins (IgG, IgA, IgM, IgE), albumin, HHV-8 viral load, and HIV testing. 1

Essential First-Tier Laboratory Tests

The following laboratory tests should be ordered for any patient with suspected Castleman disease:

Inflammatory Markers and Cytokines

  • Interleukin-6 (IL-6) levels are critical as IL-6 is the primary driver of disease manifestations in most Castleman disease subtypes 1, 2
  • C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are typically markedly elevated and serve as diagnostic criteria 1, 3
  • Interleukin-10 can be measured when available, as it is often elevated in multicentric Castleman disease 1

Complete Blood Count and Peripheral Smear

  • Complete blood count with differential to assess for anemia, thrombocytopenia, or thrombocytosis 1, 3
  • Peripheral blood smear review for morphologic abnormalities 1
  • Anemia is common in idiopathic multicentric Castleman disease (iMCD), particularly the IPL subtype 2, 3
  • Thrombocytopenia is a hallmark of iMCD-TAFRO subtype, while thrombocytosis can occur in other variants 2, 3

Metabolic and Organ Function Assessment

  • Comprehensive metabolic panel including liver function tests, renal function (creatinine, BUN), and electrolytes to evaluate organ involvement 1, 3
  • Albumin levels, as hypoalbuminemia is a minor diagnostic criterion for iMCD 1, 3
  • Lactate dehydrogenase (LDH) as a marker of disease activity 1
  • Renal dysfunction or proteinuria assessment is essential, particularly for iMCD-TAFRO subtype 2, 3

Immunoglobulin and Protein Studies

  • Serum protein electrophoresis with quantitative immunoglobulins (IgG, IgA, IgM, IgE) 1, 3
  • Polyclonal hypergammaglobulinemia is characteristic, especially in iMCD-IPL subtype 2, 3
  • IgG4 levels should be measured, as elevated IgG4 in serum and lymph node tissue can occur in iMCD-IPL and may mimic IgG4-related disease 2
  • Monoclonal paraprotein (M-component) assessment to distinguish MCD-POEMS variant 2, 4

Viral Testing

  • HHV-8 serum viral load is mandatory to distinguish HHV-8-positive MCD from idiopathic MCD, as this fundamentally changes management 1, 2
  • HIV testing is recommended if HIV status is unknown, as HHV-8-positive MCD is strongly associated with HIV infection 1, 4

Additional Markers

  • Vitamin B12 levels should be checked as part of the comprehensive workup 1
  • Circulating immune complexes may be elevated, particularly in HHV-8-positive MCD 4

Critical Diagnostic Considerations

Distinguishing Subtypes

The laboratory profile helps distinguish between Castleman disease subtypes:

  • iMCD-TAFRO: Severe thrombocytopenia, anasarca, acute kidney injury, normal or mildly elevated immunoglobulins, rapid onset cytokine storm 2, 3
  • iMCD-IPL: Anemia of inflammation, polyclonal hypergammaglobulinemia (often with elevated IgG4), subacute or chronic presentation 2, 3
  • HHV-8-positive MCD: Positive HHV-8 viral load, often HIV-positive, hypergammaglobulinemia, M-component may be present 1, 2, 4
  • MCD-POEMS: Monoclonal paraprotein, polyneuropathy, organomegaly, endocrinopathy, skin changes 2, 5

Common Diagnostic Pitfalls

  • Do not rely on histopathology alone: Castleman-like changes can occur in reactive lymph nodes from autoimmune disease, lymphoma, and infections; histologic findings must be combined with clinical and laboratory findings 2, 3
  • Exclude mimics systematically: The laboratory workup must exclude lymphoma, autoimmune conditions (particularly IgG4-related disease), infections, and hemophagocytic lymphohistiocytosis, which can present with similar laboratory abnormalities 2, 5, 3
  • Recognize heterogeneity: iMCD presents with heterogeneous symptomatology, and not all laboratory abnormalities will be present in every case 2, 3
  • At least 2 of 11 minor criteria (including at least 1 laboratory abnormality) are required for iMCD diagnosis per international consensus criteria 3

References

1
Guideline

Laboratory Evaluation for Suspected Castleman Disease

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

2
Research

Expert Perspective: Diagnosis and Treatment of Castleman Disease.

Arthritis & rheumatology (Hoboken, N.J.), 2025

4
Research

Human Herpesvirus Type 8-positive Multicentric Castleman Disease.

Clinical lymphoma, myeloma & leukemia, 2016

5
Research

Castleman disease: the great mimic.

Radiographics : a review publication of the Radiological Society of North America, Inc, 2011

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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