Abstract
The excessive release of inflammatory cytokines occasionally induces life-threatening hemophagocytosis referred to as hemophagocytic syndrome (HPS). A similar condition, histiocytic hyperplasia with hemophagocytosis (HHH), is often seen in bone marrow collected during autopsy. Unlike HPS, the pathogenesis of HHH remains unclear. Therefore, we performed a clinicopathological analysis of HHH from 70 autopsy cases at the University of Fukui Hospital. HHH was detected in 29 of 70 autopsies (41.4 %) and was significantly complicated with hematological diseases (p < 0.05) and sepsis (p < 0.05). The percentage of macrophages in bone marrow (BM) nucleated cells was significantly increased in HHH (p < 0.001). Data from medical records indicated no significant changes, except for the minimum values of white blood cell counts (p < 0.05) and platelet counts (p < 0.05) in HHH patients as compared with non-HHH patients. Concentrations of inflammatory mediators including IL-1β, IL-6, and IL-8 were significantly increased in HHH patients. Multivariate risk factor analysis identified hematological diseases (odds ratio (OR), 11.71), ≥ 15 % BM macrophages (OR, 9.42), sepsis (OR, 7.77), and high serum IL-6 levels (OR, 1.00) as independent risk factors for HHH. HHH with hypocellular BM, the most aggressive form of HHH, was recognized in 8 of 29 HHH patients and was associated with ≥ 25 % BM macrophages (p < 0.001), leukocytopenia (p < 0.05), and high IL-8 levels (p < 0.05). None of the HHH patients fulfilled the diagnostic criteria of HPS. These findings suggest that HHH is a different entity from HPS and that it preferentially develops under conditions of excessive inflammation and its associated risks, such as hematological diseases and sepsis.