A case of eosinophilic disorder that evolved in acute lymphoblastyc leukemia
Authors: Alvise Schiavinato, Elisa Piva, Giorgia Pantano, Paola Cornoldi, Mitja Nabergoj, Mario Plebani
Journal: American Journal of Hematology (2015)

A 45-year-old male blood donor was found to have leukocytosis (14.85 109/L, normal range 4.40–11.00) with an absolute eosinophil count of 9.55 109/L (normal range 0.00–0.50). ADVIA 2120i (Siemens Healthcare Diagnostics, Milan, Italy) analysis showed that eosinophils had normal mieloperoxidase activity (Image 1A left). In the peripheral blood film, the eosinophils showed morphological abnormalities, including nonlobed nuclei and partially agranular defects with a clear area of cytoplasm. (Image 1A right). Ten days later, a repeated CBC showed absolute eosinophilia (5.99 109/L), a slightly reduced Hb (128 g/L vs the initial 139 g/L, normal range 140–175 g/L) and morphologically abnormal eosinophils (Image 1B). Total IgE levels were within the normal range, fecal eosinophils, and parasites were negative. Patient was lost to follow-up and presented 6 months later complaining of fever and night sweats: WBC count was normal (4.6 109/L) as was the eosinophil count (0.02 109/L); Hb had decreased to 101 g/L, platelets to 79 109/L, and neutrophils to 0.90 109/L (normal range 1.80–7.80). Peripheral blood film examination showed the presence of agranular blasts, with a feature of lymphoblast (20%) (Image 1C). Flow cytometric immunophenotyping confirmed the presence of a CD45-, CD34+, CD19+, CD10+ bright; CD20+ dim population. Bone marrow biopsy showed hypercellularity with blasts representing the vast majority of the cells (Image 1D). Molecular analysis was performed, with no BCR/ABL, FIP1L1/PDGFRA or IGH/MYC fusion genes found. The cells had clonal abnormalities, described as three copies of SCFD2, LNX, and PDGFRA in 48% of cells, and further abnormalities of IGH gene were found in 30% of cells. In agreement with the negative FIP1L1/PDGFRA screening, serum tryptase level was normal. The case was classified as acute common lymphoblastic leukemia (LLA), developed from a chronic eosinophilic leukemia not otherwise specified (CEL-NOS). Although acute transformation has already been described as a possible clinical outcome for CEL-NOS, LLA transformation has rarely been reported 1. Primary eosinophilias encompass a group of hematologic disorders with potential for end-organ damage and acute transformation. 2. This case highlights the importance of performing a careful morphologic evaluation of the peripheral blood in the presence of eosinophilia: abnormalities like granulation defects with clear areas of cytoplasm or nuclear defects such as hyposegmentation should be evaluated and followed-up clinically and with additional laboratory investigations. (A) On the left, ADVIA 2120i cytograms (“Perox” i.e., peroxidase and “Baso” i.e., basophils channels). In the first plot, forward light scattering (x) and intensity of peroxidase activity (y) are plotted with the expandend eosinophil cluster showing normal peroxidase activity (white arrow). In the second plot for the basophil/lobularity channel eosinophils are clustered in the typicall “belly” next to the separation threshold. On the right two panels, dysmorphic eosinophils from the peripheral blood of the patient. (B) Peripheral eosinophils with nuclear and cytoplasmatic abnormalities as described in the text. (C) On the left, ADVIA 2120i cytograms (Perox and Baso channels). Reduction of eosinophils in the peroxidase scatter plot and the appearance of a new mononuclear cells population in the basophil/lobularity channel likely reflecting the presence of blasts in the peripheral blood (white arrow). On the right, blasts from the peripheral blood of the patient. (D) Bone marrow biopsy showing blast cells infiltration.