What are the guidelines for diagnosing Castleman disease?

Guidelines for Diagnosing Castleman Disease

The diagnosis of Castleman disease requires a comprehensive approach including histopathological examination of lymph node tissue, clinical presentation assessment, and radiographic evaluation to classify it as unicentric or multicentric disease. 1, 2

Classification of Castleman Disease

• Castleman disease is classified into two main types based on lymph node involvement: unicentric (UCD) and multicentric (MCD) forms 1
• Multicentric Castleman disease is further divided into HHV-8-associated and idiopathic forms 1
• The idiopathic MCD (iMCD) can be subtyped into three categories: iMCD-TAFRO (thrombocytopenia, anasarca, fever, renal dysfunction/reticulin fibrosis, organomegaly), iMCD-IPL (idiopathic plasmacytic lymphadenopathy), and iMCD-NOS (not otherwise specified) 3

Diagnostic Approach

Required Histopathological Evaluation

• Excisional lymph node biopsy is essential for diagnosis, showing characteristic histopathological features including "onion skin" and "lollipop" appearances 4, 3
• Immunohistochemical staining should include CD20 positivity assessment and HHV-8 testing 4
• Three main histopathological variants exist: hyaline-vascular, plasma cell, and mixed type 2, 5

Laboratory Evaluation

• Complete blood count with differential to assess for cytopenias or other hematologic abnormalities 1
• Inflammatory markers (ESR, CRP) to evaluate systemic inflammation 1
• HHV-8 testing is mandatory to distinguish between HHV-8-associated and idiopathic forms 1, 5
• HIV testing is recommended for all patients with suspected Castleman disease 1
• Consider testing for monoclonal proteins, especially in cases with POEMS syndrome features 1, 3

Imaging Studies

• For unicentric disease: CT or MRI to identify the single affected lymph node station 2
• For multicentric disease: PET-CT or whole-body CT to assess the extent of lymphadenopathy 2, 3
• Bone scan may be helpful in identifying characteristic bone lesions in cases with suspected POEMS association 1

Differential Diagnosis Considerations

• Lymphoma (both Hodgkin and non-Hodgkin) must be excluded through careful histopathological examination 3, 6
• IgG4-related disease can mimic Castleman disease, particularly the iMCD-IPL subtype 3
• Autoimmune conditions can present with Castleman-like lymph node changes 3
• Infections can cause reactive lymphadenopathy that may resemble Castleman disease histologically 3, 6

Special Diagnostic Considerations

• POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes) may be associated with Castleman disease and requires specific diagnostic workup 1, 3
• Kaposi sarcoma should be considered in HHV-8-positive cases, particularly in HIV-positive patients 1, 5
• Clinical findings must be correlated with histopathological features, as reactive lymph nodes in other conditions can show Castleman-like changes 3

Follow-up Recommendations

• Clinical follow-up every 3-6 months is recommended after diagnosis 1
• Monitoring should focus on disease relapse, development of non-Hodgkin lymphoma, and progression of associated conditions like Kaposi sarcoma 1
• Long-term follow-up is crucial due to the risk of malignant transformation, particularly in multicentric disease 4

Common Pitfalls in Diagnosis

• Relying solely on histopathology without clinical correlation can lead to misdiagnosis 3
• Failure to test for HHV-8 and HIV status may result in inappropriate classification and treatment 1, 5
• Unicentric disease in unusual locations (like pelvic region) may be misdiagnosed as other conditions 4
• Incomplete imaging workup may fail to distinguish between unicentric and multicentric disease 2