Abstract Introduction Kaposi sarcoma (KS) is a multifocal angioproliferative malignancy of endothelial origin driven by human herpesvirus-8 (HHV-8), also known as Kaposi sarcoma-associated herpesvirus (KSHV). The epidemic form occurs with advanced HIV and typically presents with mucocutaneous lesions. Pleural involvement is rare and often mimics infection or malignancy, particularly in people living with HIV. Distinguishing infection from malignancy in persistent pleural effusions is critical to avoid delays in oncologic care. Case Report A 30-year-old man with advanced HIV, KS, and HHV-8-associated multicentric Castleman disease complicated by HLH (diagnosed April 2024; treated with rituximab, dexamethasone, and etoposide) re-presented in August 2025 with several months of cough and dyspnea. Imaging revealed a new, loculated left pleural effusion. He was adherent to antiretroviral therapy with a CD4 count of 294 cells/µL (20.4%). On admission he was afebrile without leukocytosis. Non-contrast CT suggested empyema, and empiric vancomycin/cefepime were started. Thoracentesis was nondiagnostic; two chest tubes produced minimal output and dislodged. Pleural fluid was grossly bloody (44,000 WBCs; 92% neutrophils); bacterial, fungal, and AFB cultures and cytology were negative. On August 18 he underwent VATS with lysis, decortication, and pleural biopsies, which showed atypical vascular proliferation consistent with KS. Antibiotics were stopped, and hematology initiated liposomal doxorubicin 20 mg/m² every 3 weeks. He continued antiretroviral therapy and was discharged stable. Discussion Pleural KS is uncommon but clinically significant because its radiologic and fluid features mimic empyema and HHV-8-related primary effusion lymphoma. In advanced HIV with KS, pleuropulmonary involvement occurs in ∼20%, and ∼62% of those have effusions, usually with cutaneous disease. However, 15% present without skin lesions, leading to diagnostic delays. In HIV/HHV-8 coinfection, clues to malignancy include unilateral, loculated, or hemorrhagic effusions; persistent culture negativity; absence of systemic inflammation despite neutrophil-predominant exudates; and coexisting HHV-8-driven disorders (Multicentric Castleman disease, Primary Effusion Lymphoma, Kaposi Sarcoma Inflammatory Cytokine Syndrome). When infection is unconfirmed, early tissue sampling is essential. Cytology is often non-diagnostic, whereas thoracoscopic biopsy provides the highest yield and enables therapeutic adhesiolysis when loculations hinder drainage. This case highlights these principles: afebrile presentation, negative cultures, and recurrent bloody fluid prompted biopsy confirming pleural KS, allowing timely chemotherapy. Conclusion In immunocompromised patients—especially with HHV-8-associated disease—persistent, culture-negative, loculated effusions warrant early thoracoscopic biopsy and inclusion of pleural KS in the differential to expedite cancer-directed therapy. This abstract is funded by: None
Arikawa et al. (Fri,) studied this question.