Diagnostic Challenges in HHV-8-Associated Multicentric Castleman’s Disease in a Patient with Prior Kaposi Sarcoma

Human herpesvirus-8 (HHV-8)–associated multicentric Castleman disease (MCD) is a rare lymphoproliferative disorder that can be difficult to diagnose, particularly in immunocompromised patients. We present the case of a middle-aged man with HIV and a history of Kaposi sarcoma who developed fatigue, night sweats, polyclonal gammopathy, and diffuse lymphadenopathy shortly after treatment for Guillain-Barré syndrome. An initial core lymph node biopsy was non-diagnostic, prompting an excisional biopsy that ultimately confirmed HHV-8–positive MCD. He was started on rituximab and experienced marked clinical improvement. This case highlights the importance of considering MCD in patients with persistent systemic symptoms and known risk factors, and it underscores the limitations of core biopsy in such cases. Timely excisional biopsy can be critical for making the diagnosis and initiating appropriate treatment.