Langerhans cell histiocytosis in adults: more questions than answers?

Langerhans cell histiocytosis (LCH) may affect patients of any age but in adults the features of this disease are still poorly defined. Most reports are based on single-specialty experience and there are only a few describing relatively large series of patients. Although child and adult patients share several features of the disease, and may either have localised or disseminated disease, the proportion of cases with lung involvement is much higher in adults and is partly explained by cigarette smoking. Persisting uncertainty about the pathogenesis of LCH has certainly limited current treatment alternatives. In particular, no clinical trial has been conducted in adults so far and most information derives from description of one or a few cases, often reported retrospectively. On the basis of the background provided by the data collected in its International Registry, the Histiocyte Society is about to start the first prospective, cooperative adult LCH study, aimed at: (a) establishing a common platform for clinical evaluation; (b) testing in adult patients the efficacy of the best standard chemotherapy regimen for children-a combination of prednisone and vinblastine-developed by the Society's trials; (c) describing the natural history of the disease, the impact of cigarette smoking withdrawal and the efficacy of steroid monotherapy in pulmonary LCH. Research studies, ancillary to this trial, offer unique opportunities of addressing some of the open questions in LCH including: the genetic component of the disease as supported by evidence of familial clustering and chromosomal instability, the issue of 'LCH cells' clonality, the relation between pulmonary disease, cigarette smoking, and immune system polymorphisms that might increase individual susceptibility to LCH. A concerted joint effort between paediatricians and adult specialists could be the key to the development of insights into LCH in all age groups affected by this distressing and often debilitating condition.