Hypereosinophilic syndrome due to ETV6/PDGFR-beta gene translocation - a diagnostic and therapeutic challenge

P. Morais Silva, A.C. Costa, M. Lurdes Guerra, M. Pereira-Barbosa

Hypereosinophilic syndromes are characterized by sustained overproduction of eosinophils, leading to eosinophilic infiltration, mediator release and multi-organ damage.
Case report. A 67 year old male was referred to our Department for investigation of a persistent mild-to-moderate eosinophilia, identified 10 years previously and unresponsive to corticosteroid treatment. No other alterations were present in his differential blood count and physical examination was unremarkable. Allergic, rheumatologic and iatrogenic causes of eosinophilia were excluded by clinical history, skin-prick tests and blood and stool analysis. Iliac crest bone marrow aspiration and biopsy were performed, revealing normal cellularity with an increased eosinophil count (6%). RT-PCR of the aspirate revealed the presence of transcripts of ETV6/PDGFR-beta t(5;12) gene fusion. Karyotype analysis was normal and no mutation in PDFGR-alpha was identified. There was no evidence in analytic or imaging studies of cardiac, skin, neurologic, pulmonary or splenic involvement. A skin biopsy showed no evidence of pathologic infiltration. Initially the patient was treated with a 100 mg daily dose of imatinib mesylate, a specific inhibitor of the tyrosine-kinase domain of PDGFR. Subsequently, the daily dosage was increased to 200 mg/day to obtain eosinophil count normalization. Currently, he is under monthly hematologic and hepatic function screening. No drug side effects have been reported.
Conclusion. This patient was diagnosed with a rare myeloproliferative variant of hypereosinophilic syndrome due to a t(5;12) ETV6/PDGFR-beta translocation. Imatinib mesylate, previously used successfully in syndromes associated with PDFGR-alpha mutations, showed efficacy in the context of this mutation as well.
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