Langerhans cell histiocytosis (LCH) is a rare disorder with heterogeneous clinical manifestations (Aricò and Egeler, 1998). A continuous effort by the clinical investigators, especially in the pediatric field, has led to improved, standardized definitions of the clinical and pathologic diagnostic criteria (Chu et al., 1987; Broadbent et al., 1989; Favara et al., 1997). On this basis, better comparison of pathological and clinical data, including retrospective evaluation of large series of patients, has improved our clinical knowledge of LCH, including the isolated or uncommon manifestations (The French LCH Study Group, 1996; Willis et al., 1996). Moreover, this has been the basis for development of multicenter, international prospective clinical trials, producing definition of standard treatment for LCH in children (Gadner et al., 2001).

Over a century after the first reports, despite these recent advances in clinical management and some very interesting findings from basic research, LCH remains an intriguing disease with many unanswered questions. The etiology and pathogenesis remain largely undefined, and we still are unable to understand why it has such heterogeneous clinical behavior in the absence of identifiable differences in pathology of involved tissues. Although localized skin or bone disease is usually regarded as a benign, self-healing disease, there is a continuing debate as to the possible neoplastic origin of the disseminated form of LCH, which can be associated with a severe course and a high mortality rate (Gadner et al., 2001).