Cytogenetic abnormalities in PHA-stimulated lymphocytes from patients withLangerhans cell histiocytosis

The aetiopathogenesis of Langerhans cell histiocytosis (LCH) is still undef ined. Constitutional abnormalities in LCH have rarely been reported. One st udy showed chromosomal instability in lesional cells from three patients. N o chromosomal studies are available on peripheral blood lymphocytes. Periph eral blood lymphocytes were analysed for the presence of chromatid and/or c hromosomal breaks and structural rearrangements. A fluorescence in situ hyb ridization (FISK) painting technique was also applied in two cases. Sixteen patients with multisystem (MS, n = 11) or single system (SS, n = 5) LCH we re studied, either at the diagnosis (n = 8), during treatment (n = 2) or du ring follow-up, when asymptomatic (n = 6). Thirteen patients had chromosoma l abnormalities. Eleven patients (69%) had chromatid and chromosomal breaks in 7-45% of cells. Overall, chromosome and chromatid breaks were significa ntly more frequent in the 11 patients with MS disease than in the five pati ents with SS disease: the mean percentage of cells showing chromosome and c hromatid breaks was 13.4% in MS patients vs. 6.2% in SS patients (P = 0.003 ). Chromosomal abnormalities may be found in phytohaemagglutinin (PHA)-stim ulated peripheral blood lymphocytes of LCH patients at diagnosis, during th e disease course and even during long-term follow-up, more frequently in RA S disease. Chromosome instability may be considered as either a basic genet ic instability or as a landmark of reaction to an environmental agent (vira l?) that, through genome alteration, may play a role in histiocyte prolifer ation and, in some cases, also in the increased risk of malignancy.