Severe Eosinophilia Associated with FIP1L1/PDGFRA Rearrangement Presenting with Yamaguchi Syndrome

Abstract

FIP1L1/PDGFRA is a rare genetic rearrangement, presenting most commonly as Chronic Eosinophilic Leukemia (CEL), but may also be associated with other myeloid and lymphoid neoplasms. The peripheral blood and bone marrow exhibit a striking eosinophilia, often associated with an increased number of mast cells on trephine biopsy. Tissue infiltration by eosinophils and release of cytokines from eosinophilic granules mediate multi-organ tissue damage. The tyrosine kinase inhibitor Imatinib has been shown to induce rapid and complete clinical and haematological responses in patients harboring the mutation. We present the case of a young patient with CEL associated with PDGFRA rearrangement, presenting with severe eosinophilia and evidence of multi-organ damage (cardiac, renal, endocrine and respiratory). The peripheral blood and bone marrow displayed a striking eosinophila, and FISH analysis for FIP1L1/PDGFRA revealed a positive fusion signal in 92% of the nuclei examined. Echocardiography showed left ventricular apical hypertrophy (Yamaguchi syndrome), which has previously not been reported in this subset of patients. He was managed with supportive care, along with low-dose imatinib (100mg/day initially), to which he achieved a rapid clinical and haematological response. Currently, five months from the initial diagnosis, he is doing well on low dose imatinib (100 mg) twice a week.