An 80-year-old Hispanic female with a past medical history of diabetes mellitus, hypertension, and hyperlipidemia was referred to the hematology-oncology clinic for evaluation of anemia, leukocytosis, and eosinophilia. Her original complete blood count (CBC) showed a white blood cell (WBC) count of 15k/microL with 4.8k/microL absolute eosinophil count (AEC), hemoglobin (Hgb) of 11.3 g/dL, hematocrit (Hct) of 35.1%, mean corpuscular volume (MCV) of 95.5 FL, red blood cells (RBCs) of 3.68 million/microL, and platelets of 301k/microL. During her examination in the oncology clinic, she denied weight loss, night sweats, and fevers and had no physical exam signs of hepatosplenomegaly or rashes.
A bone marrow biopsy was performed. At the time of bone marrow biopsy, her blood cell counts showed a Hgb of 11.1 g/dL, 222k/microL, a WBC count of 13.6k/microL with a manual differential of 42% eosinophils (AEC of 6.3k/microL; image of peripheral blood eosinophils in Figure 1(a)). Bone marrow biopsy showed a hypercellular marrow for age (60% cellularity) with trilineage hematopoiesis and eosinophilia (19%) (Figure 1(b)). Iron stain on the aspirate smear showed increased ringed sideroblasts (Figure 1(c)). No evidence of reticulin fibrosis was identified by silver stain. Mild dysmegakaryopoeisis was identified. Mild megaloblastoid changes in some erythroid precursors were present.
Molecular studies were performed using a targeted myeloid panel by next generation sequencing (NGS) technology analyzing gene mutations including ASXL1, BCOR, BRAF, CALR, CBL, CEBPA, CSF3R, DDX41, DNMT3A, ETNK1, ETV6, EZH2, GATA2, GNAS, GNB1, IDH1, IDH2, JAK2, KIT, KRAS, MPL, NF1, NPM1, NRAS, PDGFRA, PHF6, PPM1D, PTPN11, RAD21, RUNX1, SETBP1, SF3B1, SH2B3, SMC1A, SMC3, SRSF2, STAG2, STAT3, STAT5B, TET2, TP53, U2AF1, WT1, and ZRSR2. Results of sequencing revealed an ASXL1 nonsense mutation, a SRSF2 missense mutation, a TET2 frameshift mutation, and a TP53 missense mutation (see Table 1). Cytogenetic analysis performed showed a normal female karyotype [46,XX]. Fluorescent in situ hybridization (FISH) was performed for PDGFRA/B and FGFR1 rearrangements and were negative. In addition to the sequencing of JAK2 in the NGS panel, polymerase chain reaction (PCR) for JAK2 (V617F) was also performed and was negative for the mutation. At this time, the differential diagnosis included CEL, NOS, and MDS with increased ringed sideroblasts associated with eosinophilia. The patient was closely followed:without medical treatment.
The patient presented with diarrhea 9 months after initial work-up. The diarrhea occured approximately two times a week containing loose stools and typically followed a meal. Stool studies for infectious etiologies were performed and were negative. Colonoscopy with random site biopsy showed microscopic colitis with lymphocytic and eosinophilic infiltration and eosinophilic cryptitis (see Figure 1(d)). The diarrhea symptoms resolved after 3 weeks of oral 9 mg budesonide treatment. No additional chemotherapy treatment was given at this time for the patient's eosinophilia.
Two years after initial presentation, the patient's WBC count increased as well as the AEC. A second bone marrow biopsy was performed to rule out disease progression and showed markedly hypercellular marrow for age (95%) with marked eosinophilia (Figure 1(e) and (f)). Given the patient's clinical course, colonic tissue infiltration by eosinophils, bone marrow morphologic findings and gene mutations identified by NGS, a diagnosis of chronic eosinophilic leukemia, NOS was made. A cardiac magnetic resonance imaging (MRI) was performed due to a new second-degree heart block to rule out eosinophilic infiltration. The cardiac MRI was negative for eosinophilic infiltration and the heart block was ruled idiopathic as her ventricle sizes were normal with an ejection fraction of 63%. No further work-up was performed for the new onset of heart block. The patient continued to be closely monitored without interferon, hydroxyurea, or any chemotherapy treatment.
A third bone marrow biopsy was performed 39 months after initial presentation. The peripheral smear associated with this bone marrow showed 2% circulating blasts with a leukocytosis consisting of eosinophilia (11%, absolute count 4.7k/microL), neutrophilia (absolute count 24.8k/microL), and monocytosis (absolute count 3.9k/microL). Macrocytic anemia (Hgb 9.5 g/dL and MCV 106.4 fL H) and mild thrombocytopenia was also present (143k/microL). Bone marrow aspirate smears show a blast count of 6% with increased eosinophils (15%). There was decreased storage iron present with 40% ringed sideroblasts. Trilineage dyspoeisis was present. Cytogenetics of the most recent bone marrow showed Trisomy 8, 13, and 14, suggesting disease progression (please refer Table 2 for information about disease course). The patient has not taken any chemotherapy agents during her follow-up care for her CEL, NOS to date.