Malignant histiocytoses

Abstract

The malignant histiocytoses are a rare group of neoplasms composed of the following histologies: histiocytic sarcoma, Langerhans cell sarcoma, interdigitating dendritic cell sarcoma, and indeterminate dendritic cell tumor. The malignant histiocytoses frequently present concurrently with other neoplasms, particularly hematological neoplasms, although they can also occur as stand-alone entities. The biology of the malignant histiocytoses remains to be completely elucidated, but in recent years there have been some very important advances. Mutations in the RAS/RAF pathway that are so important in other histiocyte disorders such as Erdheim-Chester disease and Langerhans cell histiocytosis are less common in the malignant histiocytoses but still demonstrable in a subset of cases. As in other histiocyte disorders, mutations in the RAS/RAF pathway represent a possible therapeutic target for the malignant histiocytoses. Overall, however, the optimal management of these diseases remains unclear. Surgical resection and/or radiation may be effective in localized disease, but cytotoxic chemotherapy remains largely ineffective for advance-stage disease. A further complicating matter is the fact that many patients have a concomitant hematological neoplasm that may require therapies that differ greatly from those used in the treatment of malignant histiocytoses. The identification of novel targets and further elucidation of the biology of these diseases remain critical to making therapeutic advances. This chapter will review the current literature on the epidemiology, biology, and treatment of these rare but fascinating diseases.