Langerhans cell histiocytosis: malignancy or inflammatory disorder doing a great job of imitating one?

Abstract

Langerhans cell histiocytosis (LCH) is the unifying designation for a rare proliferative disorder that occurs predominantly in childhood and involves the main antigen-presenting cell of the epidermis. LCH can present in a multitude of ways, from a self-limited rash that resolves spontaneously to a systemic multi-organ disease with a 20% mortality rate. Because some forms behave in a relatively benign manner and are associated with an inflammatory cell infiltrate, it has been proposed that LCH might be a reactive disease. However, its neoplastic nature is suggested by the fact that the proliferating cells in LCH are clonal and overexpress p53. Nonetheless, no recurrent genomic, genetic or epigenetic abnormalities have been identified. Instead, a variety of molecular abnormalities that are consistent with disordered Langerhans cell maturation have been described. A faithful small animal model would aid our understanding of the pathophysiology of LCH but, to date, none exists. Challenges to the creation of a model include the lack of characteristically recurrent genetic abnormalities and the absence of a truly tissue-specific promoter to drive expression of genetic elements solely in Langerhans cells. Still, some of the phenotypic abnormalities in adhesion molecule or chemokine receptor expression might be modeled with sufficient precision to allow the testing of novel therapies.