of malignant histiocytosis (MH) should be reserved for those patients with rapidly progressing tumors. The recent identification of frequent chromosomal gains and losses in MH, in contrast to LCH, which usually is karyotypically normal and has ,5 somatic mutations, points to the potential usefulness of molecular genetic techniques in resolving difficult cases.7 Secondary proliferations of malignant histiocytes have been identified in association with other hematologic malignancies. In some cases, a clonal relationship to the primary malignancy has been established using immunoglobulin gene rearrangement studies, BRAF mutational analysis, or another translocation or chromosomal abnormality between the primary and secondary malignancies.
8The R group, which consists in large part of Rosai-Dorfman disease, is usually straightforward diagnostically because of the characteristic cytomorphologic and immunophenotypic properties of the histiocytes. However, caution should be exercised in central nervous system disease, in which the clinical and radiographic appearance can simulate meningioma, and in cases with large numbers of IgG4 1 plasma cells, in which IgG4-related disease must be excluded.
9Entities included in the H (hemophagocytic lymphohistiocytosis [HLH]) group share the common clinical features of uncontrolled immune activation including fever, cytopenias, hepatosplenomegaly, and hyperferritinemia. Primary HLH is related to known inherited immune disorders with dysregulation of the inflammasome. Secondary HLH may be associated or triggered by an infection, connective tissue disorder, or malignancy. Interestingly, some cases of secondary HLH have recently been associated with mutations which impair cytolysis, potentially blurring the distinction between primary and secondary HLH.
10In summary, the authors and the HS are to be commended for their efforts to synthesize the ;100 categories of histiocyte disorders into a useful, informative, and up-to-date classification schema that includes practical recommendations for the diagnostician and the results of recent research in the field. And sometimes, the answers reveal more questions.Conflict-of-interest disclosure: The author declares no competing financial interests. n