Comparative study of clinical features, pathology, and immunophenotype between HIV-related cutaneous and visceral Kaposi’s sarcoma

Kaposi’s sarcoma (KS) remains a significant challenge in HIV-infected individuals, with visceral KS posing a greater therapeutic dilemma due to its aggressive nature compared to the cutaneous form. The differential immune microenvironment and molecular pathology underlying this clinical disparity are poorly understood. This study aimed to compare the clinicopathological and immunophenotypic characteristics between HIV-related cutaneous and visceral KS, with a focus on the PD-1/PD-L1 pathway, key regulatory molecules, and their association with HHV8 status. Clinical data from 21 patients with cutaneous KS and 14 patients with visceral KS were collected. Their clinical features, serum CD3/CD4/CD8 levels, histopathology, and immunohistochemical marker expression were analyzed and compared, and disease-free survival (DFS) was evaluated. The incidence of HIV infection duration ≤ 1 month was significantly higher in cutaneous KS than in visceral KS (P < 0.05). The mean peripheral blood CD3, CD4, and CD8 levels were higher in the cutaneous group. Immunohistochemical analysis revealed that cyclinD1, Rb, P53, HHV8, PD-1, PD-L1, and Ki-67 were more highly expressed in visceral KS than in cutaneous KS, with statistically significant differences in P53 and BCL-2 expression (P < 0.05). In the HHV8 high-expression subgroup, PD-1 and PD-L1 levels were significantly higher in visceral KS than in cutaneous KS (P < 0.05). Conversely, in the HHV8 low-expression subgroup, PD-1 and PD-L1 levels were significantly higher in cutaneous KS than in visceral KS (P < 0.05). (1) Distinct molecular profiles in the PD-1/PD-L1 pathway, cell cycle (CyclinD1/Rb), and apoptosis regulation (P53/BCL-2) differentiate cutaneous from visceral KS, underscoring their divergent aggressiveness; (2) PD-1/PD-L1 expression is critically dependent on HHV8 viral load, exhibiting opposing patterns across anatomical sites, which highlights the complex immune interplay in KS and underscores the aggressive nature of visceral disease.