FIP1L1-PDGFRA molecular analysis in the differential diagnosis of eosinophilia

Reverse transcriptase-polymerase chain reaction (RT-PCR) was used for the detection of FIP1L1-PDGFRA rearrangement and the results confirmed by direct sequencing. C-KIT-D816V mutation was analysed retrospectively by PCR and restriction-fragment-length-polymorphism (PCR-RFLP), in all cases with primary eosinophilia.Two male patients with splenomegaly carried the FIP1L1-PDGFRA rearrangement, whilst 2 others were ultimately classified as suffering from idiopathic hypereosinophlic syndrome (HES) and one from systemic mastocytosis. These patients were negative for the C-KIT-D816V mutation and received imatinib (100–400 mg daily). Patients with CEL and HES responded to imatinib and remained in complete haematological, clinical and molecular (for carriers of FIP1L1-PDGFRA rearrangement) remission for a median of 28.2 months (range: 11–54), whilst the patient with systemic mastocytosis did not respond. Interestingly, in both patients with FIP1L1-PDGFRA rearrangement, the breakpoints into PDGFRA were located within exon 12 and fused with exons 8 and 8a of FIP1L1, respectively.An early diagnosis of FIPIL1-PDGFRA-positive CEL and imatinib treatment offer to the affected patients an excellent clinical therapeutic result, avoiding undesirable morbidity. Moreover, although the molecular mechanisms underlying disease pathogenesis remain to be determined, imatinib can be effective in patients with idiopathic HES.Eosinophilia (> 0.5 × 109/L) is a common clinical finding that can be secondary to a large variety of diseases. When evaluation of eosinophilia fails to reveal an underlying disease, the diagnosis of hypereosinophilic syndrome (HES) is evocated. HES is defined by (1) eosinophilia (> 1.5 × 109/L) for more than 6 months; (2) exclusion of reactive eosinophilia caused by parasitic infections, allergies, or other known causes, as well as eosinophilia associated with neoplasias; and (3) evidence of end-organ damage [1-4]. Over the last decade, great progress has been made in unde