Service d'anatomie et de cytologie pathologiques, Hôpital Necker- Enfants malades et Université ParisV René-Descartes, Paris.
Langerhans cell histiocytosis (LCH) is a clonal proliferative disease of Langerhans cell's origin with an incidence of 1,08 per 200 000 per year for children. Its broad clinical spectrum has led to the use of several eponyms before Lichtenstein in 1953 brought evidence that these disorders were related to the same disease: histiocytosis X. Histiocytosis X was later shown to involve a clonal accumulation and/or proliferation of cells with the Langerhans cell (LC) phenotype.
Common presentation initially consists in isolated cutaneous or bone disease, children under two years presenting mainly with cutaneous disease. Either spontaneous healing or multivisceral disease may occur without known prognostic factor besides clinical follow up. Bad prognostic factors for LCH in children are an age under 2 years, the number of affected organs and existence of lung, liver or hematological dysfunction. Disseminated form of the disease is often resistant to therapy, with a mortality rate of 37 to 48 % mainly in the younger patients.
Unpredictability of outcome reflects our lack of understanding of aetiology and pathogenesis of LCH. Etiopathogeny of LCH is still unknown. Various hypotheses have been explored, mainly whether LCH is a malignant process, a result of a cellular immunity imbalance, and/or a reactive process following a viral infection. Searchs for a viral aetiology were unrewarding. Two studies have shown clonality in most forms of histiocytosis, but clonality does not necessarily indicate a malignant process and localized self healing disease is not a common feature of neoplasia. So far, no caryotypic abnormalities of the LCH cells were found. As LCH cells bear phenotypic characters of activated LC, LCH might be considered as a « reactive » or « dysimmune » disease, but there is no evidence of underlying infection or immune defects in patients.
Among cytokines, GM-CSF appears to strongly influence growth of both normal LC and LCH cells. Although not yet demonstrated, molecular abnormalities of GM-CSF, GM-CSF receptors genes or related genes may thus be implicated in physiopathogeny of the disease.
Mechanisms of migration of LCH cells are not yet understood. Expression by LCH cells of the mucosal adhesion receptor a4b7 is likely to be responsible for the digestive dissemination of LCH. Clinical dissemination and prognosis of the disease correlate with lack of E-cadherin expression. Loss of functions mediated by E-cadherin may thus play a role in the pathogeny of the disease.