Institution: Orlando Health
Additional authors:John Maksem MD, Raymond B. Franklin MD PhD, Lizardo Cerezo MD, and Mei Liang MD PhD
Session: Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB, or FGFR1
HISTORY
A forty-three year old African-American male presented with pruitis, weight loss, diarrhea, and shortness of breath. He has a ten-year history of these symptoms, along with splenomegaly, lymphadenopathy, and recurrent infections. He also has a two-year history of eosinophilia that was initially treated with Hydrea and steroids, and subsequently treated with two courses of imatinib, which provided symptomatic relief. His laboratory findings were significant for a white blood cell count of 32,800/μL with 60% eosinophils, hemoglobin of 11.3 g/dL, and platelet count of 70,000/μL. Serum tryptase was elevated to 114ng/mL, and serum IgE was elevated to 1343 kunits/L.
DETAILS
The peripheral smear showed marked eosinophilia with mature forms and occasional eosinophil myelocytes. Eosinophil morphologic abnormalities included nuclear hypersegmentation, sparse granulation with clear areas of cytoplasm, cytoplasmic vacuolation, and immature granules, which stain purplish on Romanowsky stain. There were no increased blasts. There was severe thrombocytopenia, and normochromic, normocytic anemia with polychromasia and macrocytes of the red cell lineage.
The bone marrow aspirate sample, stained with Wright-Giemsa, showed predominance of all elements of the eosinophilic series demonstrating progressive maturation, and no increase in blasts or other abnormal population.The bone marrow trephine biopsy was fixed in 10% formalin and stained with H&E. It was a hypercellular marrow (100% cellularity) with diffuse hypereosinophilia, and no increase in blasts or large immature forms.IMMUNOHISTOCHEMISTRY AND FLOW CYTOMETRY
The trephine biopsy was examined for immature myeloid cells by an immunohistochemical stain for CD34, which was not increased. There was minimal reticulin fibrosis. There were no p53 positive cells and mast cells were not increased, as identified with tryptase immunohistochemical stain. Eosinophils were negative for CD25, a marker of activation.
Flow cytometry was performed on the bone marrow aspirate, which showed an increase in the eosinophilic population. There was no increase in blasts and no other abnormal cellular population identified.CYTOGENETIC FINDINGS
Conventional cytogenetics showed normal male karyotype (46,XY[20]) in all cells examined. No Philidelphia chromosome or BCR-ABL fusion gene was identified.
FISH showed deletion at chromosome 4q12 (including CHIC2) resulting in fusion of the FIP1L1 and PDGFRA genes in 85% of the cells.INTERESTING FEATURES
This is a classic case of the rare FIP1L1-PDGFRA syndrome that presented as chronic eosinophilic leukemia.
PROPOSED DIAGNOSIS
Chronic eosinophilic leukemia with FIP1L1-PDGFRA
CONSENSUS DIAGNOSIS
Myeloid neoplasm with FIP1L1-PDGFRA rearrangement, presenting as "chronic eosinophilic leukemia"