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.Electronic supplementary materialThe online version of this article (doi:10.1007/s00428-014-1592-8) contains supplementary material, which is available to authorized users.
Highlights
The systemic release of excessive amounts of inflammatory cytokines results in severe clinical disorders such as acute respiratory distress syndrome, disseminated intravascular coagulation (DIC), septic shock, and multi-organ failure [1]
None of the hyperplasia with hemophagocytosis (HHH) patients fulfilled the diagnostic criteria of hemophagocytic syndrome (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
We found that HHH preferentially developed under conditions of excessive inflammation, including hematological diseases such as leukemia, lymphoma, and aplastic anemia and sepsis, and that its onset and severity were associated with pro-inflammatory IL-6 and IL-8, respectively
Summary
The systemic release of excessive amounts of inflammatory cytokines results in severe clinical disorders such as acute respiratory distress syndrome, disseminated intravascular coagulation (DIC), septic shock, and multi-organ failure [1]. The mononuclear–macrophage system is often dramatically activated [2], so that some patients develop a rare life-threatening syndrome called hemophagocytic syndrome (HPS) or hemophagocytic lymphohistiocytosis [3, 4]. The hallmark of HPS is sustained inflammatory cytokinemia due to genetic inheritance, infections, malignant lymphoma, and collagen diseases [3, 5, 6]. Patients with HPS develop persistent high fever, pancytopenia, hepatosplenomegaly, lymphadenopathy, and elevated levels of liver transaminases, bilirubin, lactate dehydrogenase, ferritin, and triglycerides [4, 7]. Histopathological examination reveals the presence of activated macrophages in hematopoietic organs such as bone marrow, liver, spleen, and lymph nodes, where they often engulf erythrocytes and hematopoietic nucleated cells [4]
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