AIMS: Langerhans cell histiocytosis is a rare disease with clonal proliferation of dendritic histiocytes, occurring most frequently in infancy and early childhood. In the localized form (single system), the disease is self-limiting, but in the cases of multisystem disease a third of the patients develop organ dysfunction. In these cases the prognosis is poor. Our objective has been to study the immunohistochemical expression of Fas and Fas-ligand (Fas-L) in order to determine whether the level of expression of these proteins could predict the outcome of the disease. We also wanted to determine the number of apoptotic cells to compare with the expression of Fas and Fas-L.

METHODS AND RESULTS: We analysed the expression of Fas and Fas-L in 76 infiltrates from 49 paediatric patients with Langerhans cell histiocytosis. We also compared the results with the expression of the tumour suppressor protein p53 and the number of cells in apoptosis detected with TUNEL. Langerhans cell histiocytosis cells showed strong expression of p53 and in some cases co-expression of Fas and Fas-L. The expression of Fas-L was significantly higher in infiltrates from patients with single-system disease. The actual number of pathological Langerhans cells in apoptosis as estimated by TUNEL was low.

CONCLUSIONS: The low number of TUNEL-reactive cells can be explained by the rapid turnover of apoptotic cells in the tissue, not leaving the apoptotic cells long enough in the tissue to be detected. The co-expression of Fas and Fas-L in some Langerhans cells can lead to an autocrine apoptotic shortcut, mediating the death of the double-positive cells. Our findings suggest that apoptosis mediated through the Fas/Fas-L pathway may contribute to the spontaneous regression of lesions in single-system disease. A delicate balance between autocrine death and survival of Langerhans cells may have been disturbed in patients with multisystem lesions.