Macrophage activation and hemophagocytic syndrome in Langerhans cell histiocytosis: Report of 30 cases

Macrophage activation and secondary hemophagocytic syndrome are rarely reported in association with Langerhans cell histiocytosis (LCH). The authors reviewed their pathology files for cases of LCH in which evidence of macrophage activation coexisted and report 30 such cases indicating that the association is not that rare and may even be underdiagnosed unless specifically sought. Available clinical data were collected and correlated with pathological findings. Of the 30 cases of LCH with varying degrees of macrophage activation, 29 had multisystem disease. The cases were graded from I to V on the basis of evidence for, and severity of, macrophage activation; cases in category I had evidence of fully developed hemophagocytic syndrome whereas those in category V had limited evidence of macrophage activation. There were seven cases with fully developed hemophagocytic syndrome (category I) and an additional five with hemophagocytosis and some but not all of the features of hemophagocytic syndrome (category II). Most of these 12 cases were young children with high-risk LCH and poor prognosis; 4 are known to have died. Coexisting hemophagocytic syndrome in these cases of LCH may have contributed to their poor prognosis. The association of LCH with macrophage activation, though more than coincidental, is of unknown pathogenesis, but the role of T lymphocytes and cytokines is prominent in both disorders and is presumed to link the two.