To whom should a patient with Castleman Disease, potentially with associated conditions such as Human Immunodeficiency Virus (HIV) or lymphoma, be referred for specialized care?

Castleman Disease Specialist Referral

Patients with Castleman disease should be referred to a hematologist-oncologist with expertise in lymphoproliferative disorders, and co-management with an HIV specialist is essential when HIV-positive. 1, 2

Primary Specialist Referral

• Hematologist-oncologist is the primary specialist for managing both unicentric (UCD) and multicentric Castleman disease (MCD), as they direct treatment decisions including rituximab therapy, chemotherapy, and monitoring for lymphoma development 1, 2, 3

• For unresectable UCD or any MCD, immediate referral to hematology-oncology is mandatory to initiate medical management, as these cases require systemic therapy rather than surgical intervention alone 4

Essential Co-Management Specialists

HIV Specialist (Infectious Disease)

• All patients with Castleman disease require HIV testing and should be referred to an HIV specialist if positive, as HIV-associated MCD requires concurrent antiretroviral therapy alongside cancer treatment 1, 2, 5

• The American Society of Transplantation specifically recommends HIV testing for all Castleman disease patients, making infectious disease consultation appropriate even before HIV status is confirmed 1

• HIV specialists manage drug-drug interactions between antiretroviral therapy and cancer treatments, which is critical for patient safety 6

HHV-8 Testing and Management

• HHV-8 testing must be performed as part of the diagnostic workup, as HHV-8-associated MCD requires different first-line treatment (rituximab monotherapy) compared to idiopathic MCD 1, 2, 3

• When HHV-8-positive MCD is identified, the infectious disease specialist coordinates antiretroviral therapy in HIV-positive patients while the hematologist-oncologist manages rituximab treatment 2

Additional Specialist Referrals Based on Associated Conditions

POEMS Syndrome Evaluation

• Neurology consultation is required when POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes) is suspected, as this requires specific diagnostic workup including serum VEGF monitoring 1, 5

• For POEMS-associated Castleman disease, radiation oncology should be consulted for localized disease, while systemic chemotherapy followed by autologous stem cell transplantation is coordinated by hematology-oncology for disseminated disease 1

Kaposi Sarcoma Screening

• Dermatology or oncology evaluation for Kaposi sarcoma is necessary, as this HHV-8-associated malignancy frequently coexists with MCD and requires monitoring during follow-up 6, 2

• The NCCN guidelines emphasize that unexplained fevers in Castleman disease patients should prompt workup for multicentric Castleman disease and KSHV-associated inflammatory cytokine syndrome 6

Nephrology Consultation

• Nephrology referral is indicated when immune complex-mediated membranoproliferative glomerulonephritis (MPGN) is suspected, as this can be associated with Castleman disease 1

Surgical Consultation Pathway

• Surgical oncology or general surgery should be consulted for UCD when complete surgical resection is feasible, as this is often curative and represents the preferred first-line therapy 1, 4

• For unresectable UCD causing compression of vital structures, surgery may be consulted after medical therapy (rituximab, steroids), radiotherapy, or embolization renders the lesion amenable to resection 4

Multidisciplinary Team Structure

• A multidisciplinary team with expertise in Castleman disease should include representation from hematology-oncology (primary), infectious disease (HIV/HHV-8 management), and appropriate specialty disciplines based on associated conditions 6, 7

• Clinical follow-up every 3-6 months is recommended with monitoring for disease relapse, development of non-Hodgkin lymphoma (which remains elevated despite rituximab treatment), and reactivation of concomitant Kaposi sarcoma 1, 2

Critical Pitfall to Avoid

• Do not delay referral to hematology-oncology while pursuing extensive infectious disease workup, as Castleman disease diagnosis is often delayed due to its rarity and overlap with autoimmune, inflammatory, and infectious conditions 8, 9

• Ensure excisional lymph node biopsy rather than fine-needle aspiration for definitive diagnosis, as FNA is insufficient for distinguishing Castleman disease from lymphoma 5