Clinicopathologic features of lymphoma-associated hemophagocytic lymphohistiocytosis in a multicenter adult cohort.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome that, in adults, is most commonly secondary to malignancy. Lymphoma-associated HLH (LA-HLH) is typically driven by aggressive non-Hodgkin lymphomas, while Hodgkin lymphoma is reported infrequently. We conducted a retrospective, multicenter analysis of adults diagnosed with LA-HLH between 2000 and 2024 at two tertiary academic centers. HLH diagnoses were confirmed using HLH-2004 criteria, and clinicopathologic features, laboratory findings, and outcomes were analyzed descriptively, with stratification by HIV status. Among 20 patients with LA-HLH, Hodgkin lymphoma accounted for 60% of cases. HIV-positive patients more commonly developed aggressive non-Hodgkin lymphomas with severe systemic inflammation, whereas HIV-negative patients more frequently had Hodgkin lymphoma. Soluble interleukin-2 receptor levels were uniformly elevated among evaluable patients. Overall mortality remained high. These findings are descriptive and hypothesis-generating and highlight the clinical heterogeneity of LA-HLH.