What are the differences in diagnosis and treatment between Castleman disease and Kikuchi disease?

Castleman Disease vs. Kikuchi Disease: Diagnostic and Treatment Differences

Castleman Disease (CD) and Kikuchi Disease (also known as Kikuchi-Fujimoto Disease or histiocytic necrotizing lymphadenitis) are distinct lymphoproliferative disorders with different diagnostic approaches and treatment protocols. The key differences in diagnosis and treatment between Castleman Disease and Kikuchi Disease center on their clinical presentation, histopathological features, and therapeutic management strategies, with Castleman requiring more aggressive intervention due to its potential for malignant transformation and systemic complications.

Diagnostic Differences

Clinical Presentation

Castleman Disease

• Presents in two distinct forms: unicentric CD (UCD) involving a single lymph node region and multicentric CD (MCD) involving multiple lymph node regions 1
• UCD typically presents as a single enlarged lymph node, most commonly in the mediastinum, but can occur in other locations including the pelvis 2
• MCD presents with systemic symptoms including fever, night sweats, weight loss, and multiple enlarged lymph nodes 1
• Laboratory findings may include anemia, elevated inflammatory markers, hypergammaglobulinemia, and thrombocytosis or thrombocytopenia depending on subtype 1

Kikuchi Disease

• Typically presents with cervical lymphadenopathy that is usually unilateral 3
• Lymph nodes are generally tender, 1.5-4 cm in diameter, and located in the posterior cervical triangle 3
• Often accompanied by fever and may include skin rash and mild hepatosplenomegaly 3
• Usually self-limited with spontaneous resolution within 1-4 months 3

Imaging Characteristics

Castleman Disease

• Ultrasound shows hypoechoic, well-defined, homogeneous masses with increased vascularity 2
• CT/MRI reveals homogeneous enhancement with contrast 2
• PET/CT is valuable for staging and treatment response evaluation in multicentric disease 4

Kikuchi Disease

• Ultrasound shows multiple enlarged lymph nodes, often with a preserved hilum unlike bacterial lymphadenitis which typically shows a hypoechoic core 3
• CT may show multiple enlarged nodes without necrosis 3

Histopathological Features

Castleman Disease

• Three histological variants: hyaline-vascular, plasma cell, and mixed 4
• Characteristic "onion skin" appearance of lymphoid follicles and "lollipop" lesions 2
• Immunohistochemistry shows CD20 positivity in follicular dendritic cells 2
• May be associated with HHV-8 infection in some multicentric cases 1

Kikuchi Disease

• Shows histiocytic necrotizing lymphadenitis with paracortical areas of necrosis 3
• Absence of neutrophils and presence of histiocytes and plasmacytoid dendritic cells 3
• Negative for HHV-8 and other viral markers 3

Treatment Differences

Castleman Disease Treatment

Unicentric Castleman Disease (UCD)

• Complete surgical resection is the preferred first-line therapy and is often curative 5
• For unresectable UCD:
  • Asymptomatic cases may be observed 5
  • Symptomatic cases due to compression may benefit from medical therapy (rituximab, steroids), radiotherapy, or embolization to reduce size prior to attempted resection 5
  • Anti-IL-6 therapy (siltuximab) is recommended for unresectable UCD with inflammatory syndrome 5

Multicentric Castleman Disease (MCD)

• Treatment depends on subtype (HHV-8 associated, POEMS-associated, or idiopathic) 6
• First-line therapy for idiopathic MCD is siltuximab (anti-IL-6 monoclonal antibody) with or without corticosteroids 6
• For severe cases, adjuvant combination chemotherapy is recommended 6
• Second and third-line therapies include rituximab, cytotoxic chemotherapy, immunomodulators, and targeted therapies 1
• HHV-8 positive MCD may benefit from antiviral therapy in addition to other treatments 1

Kikuchi Disease Treatment

• Generally self-limited, requiring only supportive care and observation 3
• Analgesics and antipyretics for symptomatic relief 3
• Short course of corticosteroids may be considered for severe or persistent symptoms 3
• No specific antiviral or antibiotic therapy is indicated 3
• Follow-up is essential until complete resolution 3

Prognosis and Follow-up

Castleman Disease

• UCD has excellent prognosis after complete surgical resection with cure rates approaching 100% 4
• MCD has a more guarded prognosis, particularly HHV-8 positive cases 1
• Long-term follow-up is essential due to risk of malignant transformation, particularly lymphoma 2
• The 5-year survival for treated MCD varies widely depending on subtype and treatment response 6

Kikuchi Disease

• Excellent prognosis with spontaneous resolution within 1-4 months 3
• Recurrence is rare (3-4% of cases) 3
• No increased risk of lymphoma or other malignancies 3

Important Clinical Considerations

• Castleman Disease can be associated with KSHV-associated inflammatory cytokine syndrome (KICS) and should be considered in differential diagnosis of unexplained fevers 7
• Multicentric Castleman Disease can be confused with lymphoma, IgG4-related disease, or autoimmune conditions 1
• Kikuchi Disease is often misdiagnosed as bacterial lymphadenitis, leading to unnecessary antibiotic treatment 3
• Biopsy is essential for definitive diagnosis in both conditions 3, 5
• In cases of cervical lymphadenopathy, careful examination of lymph node characteristics is crucial - multiple enlarged nodes suggest Kikuchi or Castleman, while a single node with hypoechoic core suggests bacterial infection 7