Atypical Kaposi Sarcoma in HIV Infection with Predominant Nodal Involvement.

Kaposi sarcoma (KS) is an angioproliferative neoplasm driven by human herpesvirus 8 (HHV-8), most commonly occurring in immunocompromised individuals, particularly in association with HIV infection. Although it classically presents with characteristic cutaneous or mucocutaneous lesions, nodal-predominant disease without skin involvement is uncommon and may pose a significant diagnostic challenge. We report the case of a 26-year-old man with recently diagnosed HIV infection and no prior antiretroviral therapy (ART) who presented with a two-week history of persistent fever, constitutional symptoms, abdominal pain, and progressive intolerance to oral intake. Initial evaluation revealed hemodynamic instability, severe microcytic anemia, marked thrombocytopenia, and progressive renal dysfunction. Imaging demonstrated generalized lymphadenopathy involving multiple nodal chains, bilateral pleural effusions, hepatosplenomegaly, and free intra-abdominal fluid, raising concern for a disseminated infectious, lymphoproliferative, or neoplastic process. CD4+ T-cell count and HIV viral load were not available in the clinical records reviewed; therefore, the degree of HIV-associated immunosuppression could not be quantitatively established. Given the persistence and progression of systemic manifestations, an excisional inguinal lymph node biopsy was performed. Histopathological examination demonstrated spindle-cell proliferation with irregular slit-like vascular spaces and erythrocyte extravasation. Immunohistochemical analysis showed nuclear positivity for HHV-8 latent nuclear antigen-1 (LNA-1), together with positivity for endothelial markers, confirming KS. No cutaneous or mucosal lesions suggestive of KS were identified during the clinical course, supporting an atypical presentation with predominant nodal involvement. The patient received supportive inpatient management, including hemodynamic stabilization and transfusional support. Despite an initial period of partial clinical stabilization, he subsequently developed acute respiratory failure with progressive clinical deterioration and died during the index hospitalization before the planned HIV- and KS-directed therapeutic strategy could be completed. Nodal KS without cutaneous involvement is an uncommon and potentially underrecognized presentation that may mimic HIV-associated lymphoma, disseminated opportunistic infections, and HHV-8-associated multicentric Castleman disease. This case emphasizes that KS should remain in the differential diagnosis of persistent lymphadenopathy and systemic manifestations in patients with HIV even when characteristic skin lesions are absent. Because imaging findings are nonspecific, early tissue biopsy with histopathological examination and HHV-8 immunohistochemistry is essential for definitive diagnosis. This paper was published earlier on the Research Square preprint server on April 14, 2026 (DOI: 10.21203/rs.3.rs-9363985/v1).