Langerhans cell histiocytosis: A reactive or neoplastic disease?

Abstract

Although Langerhans cell histiocytosis (LCH) was first described a century ago, the aetiology is still not understood. Recent studies on the role of cytokines, chemokines, immunologic dysfunction, cell surface antigen expression, clonality and cell cycle regulation have provided new insights into the pathogenesis of LCH. Much of the data from these studies points to the Langerhans cell (LC) being intrinsically abnormal in LCH. Studies have shown that there is a proliferation of clonal LCs in the lesions of LCH. Furthermore, these LCH cells not only have differences in cytoplasmic and surface markers compared to the normal LC but also show abnormalities in cytokine production and antigen presentation. The recent progress in LCH research has provoked much discussion on whether LCH is a reactive disease resulting from environmental triggers, or a neoplastic process. The main goal of this thesis was to gain insight into the immunological and genetic aspects of LCH. We set out to address several previously unanswered questions in LCH, namely, why are the lesional CD1a+ LCs in LCH aberrantly present in many body sites; what is the origin—whether via recruitment or in situ formation—of the many cells characteristic of the lesion composition and finally, the ultimate question of what is the cause behind this disease, a reactive trigger or a neoplastic defect.