Hemophagocytic lymphohistiocytosis and other histiocytic disorders of the bone marrow in children

Abstract

The primary functions of bone marrow histiocytes are to remove cellular debris (phagocytosis) and to store and metabolize iron. Increased bone marrow histiocytes can be seen in both non-specific reactive settings and in histiocytic disorders. One such entity, hemophagocytic lymphohistiocytosis (HLH), is a hyperinflammatory syndrome resulting from excessive and uncontrolled immune activation. Bone marrow hemophagocytosis, the ingestion/engulfment of intact nucleated cells by marrow histiocytes, is one of the diagnostic criteria of HLH, along with fever, splenomegaly, cytopenias, hypofibrinogenemia, hypertriglyceridemia, and other evidence of immune/T-cell activation. As such, bone marrow evaluation is an important component of the HLH work-up, performed to identify hemophagocytic histiocytes and to evaluate for potential triggers of immune activation, such as a hematologic malignancy. Bone marrow evaluation can also be helpful in the diagnosis of other histiocytic proliferations, such as metabolic storage disorders including Gaucher disease and Niemann-Pick disease. Increased bone marrow histiocytes may also represent involvement by histiocytic/dendritic cell neoplasms, such as Langerhans cell histiocytosis, juvenile xanthogranuloma, or ALK-positive histiocytosis. This review will examine the bone marrow findings, diagnostic work-up, and underlying causes of HLH, as well as discuss other histiocytic bone marrow proliferations that can affect the pediatric population.