Management and Treatment of Castleman Disease
Classification and Initial Approach
Castleman disease must first be classified as unicentric (UCD) or multicentric (MCD), as this fundamentally determines treatment strategy, with surgical resection being curative for UCD while MCD requires systemic therapy. 1, 2
Disease Classification
- Unicentric CD (UCD): Involves a single lymph node station, typically asymptomatic or causing localized symptoms 2, 3
- Multicentric CD (MCD): Involves multiple lymph nodes with systemic inflammatory symptoms, further subdivided into:
Essential Diagnostic Workup
- Complete blood count with differential and inflammatory markers 1
- HHV-8 testing is mandatory to distinguish MCD subtypes 1
- HIV testing is required for all patients with Castleman disease 1
- Histopathological confirmation showing characteristic "onion skin" and "lollipop" appearances 4
Treatment of Unicentric Castleman Disease
Complete surgical resection is the preferred first-line therapy for UCD and is often curative. 2, 5
Resectable UCD
- Surgical excision of the solitary mass provides excellent outcomes with 90.2% overall survival 6
- This approach is curative in most cases 2, 4
Unresectable UCD Management Algorithm
- Asymptomatic unresectable UCD: Observation is appropriate 2
- Symptomatic with inflammatory syndrome: Siltuximab (anti-IL-6 monoclonal antibody) should be considered 2
- Symptomatic from mass effect/compression: Consider medical therapy (rituximab, corticosteroids), radiotherapy, or embolization to render the mass resectable 2
Treatment of HHV-8-Associated Multicentric Castleman Disease
Rituximab monotherapy is the first-line treatment for HHV-8-associated MCD. 1, 5
Treatment Protocol
- Rituximab monotherapy as standard first-line therapy 1, 5
- Add etoposide for severe cases 1
- Cytotoxic chemotherapy should be added for patients with concomitant Kaposi sarcoma 1
- Antiretroviral therapy must always be administered in HIV-positive patients 1
Important Caveat
Rituximab treatment reduces but does not eliminate the risk of non-Hodgkin lymphoma, which remains elevated in these patients 1
Treatment of Idiopathic Multicentric Castleman Disease
Siltuximab (anti-IL-6 therapy) is the FDA and EMA-approved first-line treatment for iMCD. 3
Treatment Algorithm
- First-line: Siltuximab (anti-IL-6 monoclonal antibody therapy) 3
- For severe inflammation or inadequate response to IL-6 blockade: Triple therapy with corticosteroids, rituximab, and cyclophosphamide 1, 7
- For refractory anemia and thrombocytopenia: Splenectomy may be considered 1
Special Considerations for Renal Involvement
- Bortezomib-based regimens may be considered for patients with monoclonal immunoglobulin deposition disease components 7
- Kidney transplantation should be deferred until complete disease remission is achieved 7
Follow-Up and Monitoring
Clinical follow-up every 3-6 months is required to monitor for: 1
- Disease relapse
- Development of non-Hodgkin lymphoma (risk remains high despite treatment)
- Reactivation or progression of concomitant Kaposi sarcoma in HHV-8-positive patients
POEMS Syndrome Screening
POEMS syndrome may be associated with Castleman disease and requires specific diagnostic workup when polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, or skin changes are present 1, 3
Prognosis
- UCD: Excellent prognosis with surgical resection, 90.2% overall survival 6
- MCD: Overall survival 90.2%, but progression-free survival is significantly poorer than UCD 6
- Age ≥60 years and splenomegaly are independent adverse prognostic factors affecting both overall and progression-free survival 6
Common Pitfalls to Avoid
- Do not treat MCD with surgery alone—systemic therapy is required 2, 5
- Do not overlook HIV and HHV-8 testing—this determines treatment approach 1
- Do not discontinue monitoring after successful treatment—lymphoma risk persists 1
- Do not assume all lymphadenopathy is UCD—thorough evaluation for systemic symptoms and multiple node involvement is essential to distinguish from MCD 2, 3