Case Report: HHV8-positive multicentric Castleman disease in an HIV-positive patient :diagnostic challenges arising from atypical histology and the role of metagenomic sequencing

Background Multicentric Castleman disease (MCD), especially the HHV8-positive subtype, is a rare lymphoproliferative disorder that presents considerable diagnostic and therapeutic difficulties, particularly among HIV-positive patients. The co-occurrence of other infections, such as syphilis, may further complicate its clinical picture and management. Case description A 42-year-old man with well-controlled HIV presented with persistent fever, fatigue, and disseminated lymphadenopathy,. Through histopathological examination, molecular testing (including mNGS for HHV8), and PET-CT imaging, HHV8-positive MCD was diagnosed, along with latent syphilis. The patient was successfully treated with R-VP16 (rituximab and etoposide) for MCD and benzathine penicillin for syphilis, showing a positive clinical response. Throughout 36 months of continuous monitoring, the patient has maintained sustained complete remission with no evidence of disease recurrence. Conclusion This case underscores the importance of considering HHV8-driven lymphoproliferative disorders in HIV patients with unexplained lymphadenopathy and systemic symptoms, particularly in HHV8-endemic regions. It also highlights the essential roles of advanced diagnostics and multidisciplinary management in such complex presentations. The favorable outcome demonstrates the effectiveness of timely and targeted treatment, though long-term follow-up remains necessary due to the potential for relapse or progression.