Institution: John H Stroger Jr. Hospital of Cook County
Additional authors:Paula Kovarik, MD and Mousami Shah, MD
Session: Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB, or FGFR1
HISTORY
53 yr old male with past medical history of untreated hypertension and gunshot wounds, s/p right partial lobectomy in 1984, presented with multiple syncopal episodes, fever, drenching night sweats, cough, shortness of breath, fatigue, constipation, 35lb weight loss over 8 months, and increasing blurry vision for the past few days. Cough and SOB were reported to be worse at night/ lying flat on his back. He reported one episode of blood-tinged sputum, ppd was negative.
He was admitted at Stroger Hospital with normal vital signs and negative review of systems except for the symptoms listed in the history of present illness. CBC showed marked leukocytosis of 103.6 k/uL with a left shift and markedly increased eosinophils of 22% (FIG 1). Basophils were not seen. In addition, he had macrocytic anemia with Hgb of 8 g/dl, Hct of 27% and MCV of 102 Fl and borderline thrombocytopenia of 160 k/uL. Rare nucleated red blood cells were seen in the peripheral smear.DETAILS
He underwent a bone marrow biopsy of right posterior iliac crest (fixed in 10% buffered formalin). The aspirate was hemodilute and showed findings similar to peripheral blood. Touch imprints and bone marrow core biopsy both demonstrated hypercellular marrow for age (>90%) with marked myeloid hyperplasia (M:E=13:1) (FIG 2). The myeloid series showed maturation to neutrophils and increased numbers of mature eosinophils (30%) (FIG. 3). Blasts were not increased. In addition, the erythroid series was hypoplastic. Megakaryocytes were markedly decreased, few small hypolobated forms were seen. Special stain for reticulin showed increased reticulin fiber deposition (2+/3) (FIG 4).
IMMUNOHISTOCHEMISTRY AND FLOW CYTOMETRY
Flow cytometry of peripheral blood showed markedly expanded myeloid population including increased mature eosinophils and no increase in CD34+ blasts.
Immunostains were performed on bone marrow core biopsy. CD34 stain marks the capillaries, no increase in blasts is present. CD117 stain highlights few scattered mast cells.CYTOGENETIC FINDINGS
Complete karyotype could not be performed due to lack of dividing cells (metaphase nuclei).
MOLECULAR FINDINGS
Fluorescent in situ hybridization study, performed on peripheral blood, showed no evidence of Philadelphia chromosome t(9;22), BCR/ABL1.
Fluorescent in situ hybridization study, performed on peripheral blood, with SCFD2, LNX and PDGFRA (4q12) probes (Abbott Molecular/Vysis) exhibited a pattern of hybridization suggestive of FIP1L1-PDGFRA fusion (detected in 95% of interphase cells).INTERESTING FEATURES
This is otherwise healthy male who presents with symptoms of end organ damage due to infiltration by chronic eosinophilic leukemia (syncopy, shortness of breath, cough, fever, night sweats, weight loss). Due to the documented 4q12 rearrangement by FISH, this condition is best classified as chronic myeloproliferative neoplasm with eosinophilia and abnormality of PDGFRA. It is very sensitive to treatment with imatinib mesylate. This patient was started on Gleevec and one month later his CBC is completely normal, the eosinophilia has resolved and his symptoms are gone.
PROPOSED DIAGNOSIS
Chronic myeloproliferative neoplasm with eosinophilia and abnormality of PDGFRA (FIP1L1-PDGFRA).
CONSENSUS DIAGNOSIS
Myeloid neoplasm with FIP1L1-PDGFRA rearrangement, presenting as "chronic eosinophilic leukemia"