AIDS-Associated Hemophagocytic Syndrome: A Study of 100 Autopsy Cases
M Naghashpour, EM Sagatys, R Smith, HD Cualing. Moffitt Cancer Center and Research Institute, Tampa, FL; University of Cincinnati, Cincinnati, OH
Background: Hemophagocytic syndrome (HPS) is a clininicopathologic entity characterized by proliferation of macrophages with hemophagocytosis throughout the reticuloendothelial system. Its pathogenesis is thought to be related to defects of NK- and cytotoxic T-cells, and an altered cytokine milieu. HPS may be primary or secondary (acquired). Acquired HPS has been described in association with various infections, malignancy, collagen vascular disease and immunodefficient states. Clinical presentation is that of a systemic illness, typically characterized by fever, cytopenias and splenomegaly.
Design: A total of 100 consecutive adult AIDS autopsy records were identified. Cases with splenomegaly (>500 grams) were selected. Massive splenomegaly was defined as splenic weight >1000 grams; we prefer the term macrosplenomegaly. Tissue sections were stained by conventional histologic stains (H&E, PAS, Giemsa and silver stains) to investigate the etiology of splenomegaly. Immunohistochemical stains and in situ hybridization for viral RNA, and electronmicroscopy for the examination of utrastructure were also performed.
Results: Our analysis revealed fourteen cases with splenomegaly (14%), of which six cases showed massive splenomegaly (6%). Five of these six cases had histologic evidence of histiocytosis with hemophagocytosis in multiple organs including spleen. Mortality preceded by intractable fever, cytopenias unresponsive to blood product transfusions, and multi-organ systemic dysfunction. The clinical signs and symptoms in comibation with the morphological findings were characteristic and diagnostic of HPS. In four cases (4%), an underlying opportunistic infection (EBV and CMV) and/or a virus-associated malignancy (Kaposi sarcoma) were present. In one patient (1%), no underlying malignancy or opportunistic co-infection was found.
Conclusions: We found HPS and associated massive splenomegaly in 5 of 100 AIDS autopsy cases. In the setting of HIV infection, impaired cytotoxic T lymphocyte function, selected NK-cell depletion, and/or opportunistic infections in conjunction with an altered cytokine milieu may explain the predisposition to developing HPS. In our study, HIV infection in conjunction with opportunistic infectious agents (EBV and CMV) and/or malignancy (Kaposi sarcoma) is implicated to have precipitated 4 of 5 HPS cases. HIV infection alone (1 of 5 cases) may also trigger life-threatening HPS with associated macrosplenomegaly and severe cytopenias.
Monday, March 9, 2009 11:30 AM
Platform Session: Section G 2, Monday Morning