Kaposi sarcoma is a vascular neoplasm driven by human herpesvirus 8 (HHV-8), commonly seen in the setting of immunosuppression, such as HIV/AIDS or posttransplant therapy. The presentation of Kaposi sarcoma in HIV-negative patients with multicentric Castleman disease is exceedingly rare, particularly with uncommon histology subtypes and involvement of the penile shaft. A 58-year-old HIV-negative man with a history of HHV-8-associated multicentric Castleman disease presented with a violaceous lesion on the buttock, followed by a crusted ulcer on the penile shaft. Histopathologic evaluation of the penile biopsy revealed an atypical vascular proliferation lacking spindle cell morphology in classic Kaposi sarcoma. Immunohistochemistry showed positivity for HHV-8, podoplanin (PDPN, clone D2-40), CD34, ERG in the proliferating endothelial cells. The morphologic features and the immunoprofile were consistent with the angiomatous subtype of Kaposi sarcoma. Despite aggressive treatment, the patient progressed to multiorgan failure and died shortly after. This report contributes to the limited body of literature on HHV-8-associated Kapsoi sarcoma in the setting of multicentric Castleman disease in HIV-negative patients. It emphasizes the importance of recognizing angiomatous subtype of Kaposi sarcoma with involvement of unusual anatomical sites.

Human herpesvirus-8 (HHV-8)-associated multicentric Castleman disease (MCD) is a rare lymphoproliferative disorder with systemic and cutaneous manifestations that can be diagnostically challenging, especially in immunocompromised patients. We report the case of a 68-year-old man with HIV and biopsy-proven Kaposi sarcoma (KS), who developed progressive fevers, night sweats, weight loss, and fatigue, accompanied by diffuse lymphadenopathy, splenomegaly, and new erythematous and hyperpigmented lesions shortly after intravenous immunoglobulin therapy for Guillain-Barré syndrome. A laboratory evaluation revealed that the patient had elevated total protein and polyclonal hypergammaglobulinemia, without monoclonality. Imaging demonstrated widespread lymphadenopathy and splenomegaly. A core lymph node biopsy showed polytypic plasmacytosis, but was non-diagnostic. Given the ongoing symptoms, an excisional biopsy was performed, revealing regressed germinal centers with increased interfollicular vascularity, mantle zone "onion skinning," and HHV-8 LANA-1 nuclear positivity, establishing the diagnosis of HHV-8-associated MCD. Rituximab monotherapy was initiated, resulting in clinical improvement, resolution of the constitutional symptoms, and stabilization of ascites. This case highlights the importance of maintaining a high index of suspicion for MCD in patients with KS who develop new systemic or cutaneous findings, the limitations of a core biopsy, and the value of a timely excisional biopsy in guiding diagnosis and treatment.

Castleman disease and Kaposi sarcoma are uncommon conditions that can occur in association with human immunodeficiency virus (HIV) infection. We report a case of a 26-year-old man newly diagnosed with acquired immune deficiency syndrome who presented with fever, nocturnal chills, generalized lymphadenopathy, hepatosplenomegaly, anemia, and thrombocytopenia. Imaging revealed widespread lymphadenopathy and bone marrow hypermetabolism. Histopathological examination of an excised cervical lymph node demonstrated atrophic follicles with involuted germinal centers and an expanded mantle zone containing scattered plasmablasts - features consistent with Kaposi sarcoma herpesvirus/human herpesvirus 8 (KSHV/HHV-8)-associated multicentric Castleman disease, with microscopic foci of Kaposi sarcoma featuring spindle cell proliferation with slit-like vascular channels. Immunohistochemical staining confirmed HHV-8 positivity in plasmablasts and spindle cells of Kaposi sarcoma. This case highlights the importance of a thorough evaluation of HIV-positive patients presenting with lymphadenopathy to ensure early recognition of rare but clinically significant conditions requiring aggressive management. Recognition of concurrent HHV-8-associated Castleman disease and Kaposi sarcoma is critical, as treatment strategies differ and outcomes may be influenced by early therapeutic intervention.

The clinical and laboratory characteristics of HHV-8-associated multicentric Castleman disease (MCD) in people with HIV (PWH) overlap with those of haemophagocytic lymphohistiocytosis (HLH) disease and indeed the two diagnoses may co-exist. A risk-stratified treatment approach to MCD based on Rituximab immunotherapy for mild cases and chemo-immunotherapy for severe cases has been shown to yield excellent outcomes in PWH. In contrast, HLH disease, previously known as secondary HLH, has a dismal prognosis even when promptly treated according to guidelines. A retrospective multicentre cohort study. Retrospective analysis of prospectively collected clinical and pathological data on patients with biopsy-proven HIV-associated MCD at the National Centre for HIV Malignancy at Chelsea and Westminster Hospital, London between 2008 and 2024 and at the Department of Infectious Diseases at St. Joseph Hospital Berlin-Tempelhof, Germany between 2020 and 2024. In our UK-German cohort, including 113 PWH with MCD, we confirmed that HLH disease secondary to MCD is common (30%), and we demonstrated that HLH disease in this context does not adversely influence survival or risk of MCD relapse. We suggest that a high HScore in MCD should not lead to a change in the treatment in this specific setting.