Case 880 -- A 53-year-old male with leukocytosis and a neutrophilic left shift

Contributed by Lama Farchoukh, MD and Fiona E. Craig, MD


CLINICAL HISTORY

A 53-year-old male was found to have leukocytosis and a neutrophilic left shift on routine blood work (Image 1).

PERIPHERAL BLOOD REVIEW

Microscopic evaluation of the peripheral blood showed some circulating blasts (3.5%). The blasts were mostly large cells with basophilic cytoplasm and occasional cytoplasmic granules. A subset of blasts were smaller, had a higher nuclear/cytoplasmic ratio and agranular basophilic cytoplasm (image 2). In addition there was marked leukocytosis (image 3) and maturing neutrophilic cells (image 4).

FLOW CYTOMETRIC IMMUNOPHENOTYPIC STUDIES

Flow cytometric immunophenotypic studies performed on the peripheral blood demonstrated a population of abnormal blasts comprising approximately 5% of the total events with the following phenotype (images 5 and 6):

CD34 positive, CD45 dim positive, HLA-DR positive, CD19 positive, CD10 bright positive, TdT positive, cytoplasmic CD22 positive, CD79a positive, CD38 dim positive, CD33 dim positive, CD13 variably positive, MPO negative, CD58 negative, CD123 negative, CD64 negative, CD36 mostly negative, CD14 negative, CD16 negative, CD56 negative, CD117 negative, CD15 negative, CD11b mostly negative, CD20 mostly negative, cytoplasmic CD3 negative. In addition, there were many maturing neutrophilic cells with partial staining for CD56, a few monocytes, a few basophils, rare CD117 positive immature myeloid cells, a few heterogenous T-cells and rare polytypic B-cells.

Of note, Flow cytometric immunophenotypic studies performed on the bone marrow also demonstrated a population of abnormal blasts with similar immunophenotype comprising approximately 3.8% of the total events.

BONE MARROW REVIEW

The myeloid/erythroid ratio was markedly increased and blasts were increased (5.3%) (image 7) according to manual differential count performed on aspirate smears. The bone marrow biopsy was markedly hypercellular approaching 100% cellular (image 8) with only scattered immature appearing cells. The erythroid and myeloid maturation were complete. Megakaryocytes were present and included occasional monolobate forms. No focal lesions were identified. The bony trabeculae were unremarkable. Flow cytometric immunophenotypic studies performed on the bone marrow showed similar findings to the peripheral blood flow.

IMMUNOHISTOCHEMICAL STUDIES

In order to further enumerate the blasts, immunohistochemical stains were performed on the bone marrow biopsy and the following results were found (images 9 and 10):

ADDITIONAL STUDIES

Cytogenetic studies showed an abnormal male chromosome analysis positive for the Philadelphia chromosome 46,XY,t(9;22)(q34;q11.2)[20].

Fluorescence in situ hybridization (FISH) was positive for the BCR/ABL1 gene rearrangement in 178 of the 184 interphase cells examined (97.3%). FISH performed on a concurrent peripheral blood specimen was positive for the BCR/ABL1 gene rearrangement in (97.1%) of the interphase cells examined.

Quantitative real-time PCR for BCR/ABL1 demonstrated the BCR/ABL1 major (p210) transcript, (>10 % IS or 17.3 % relative to K562 expression) but was negative for the BCR/ABL1 minor (p190) transcript.

FINAL DIAGNOSIS


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