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A 51-year-old man with hypertension presented with left upper quadrant (LUQ) pain, fatigue, and 10 kg weight loss over 6 months. He had no fever or lymphadenopathy. Physical examination was significant for hepatomegaly palpable 6 cm below the coastal margin and spleen palpable 12 cm below the costal margin. Laboratory evaluation revealed a white blood cell (WBC) count of 206.3 × 103/uL, with 34% neutrophils, 9% blasts, 11% eosinophils, 18% basophils, 8% metamyelocytes, and 18% myelocytes. Hemoglobin level was 9.4 g/dL and platelet count was 455,000/uL. A peripheral blood smear was obtained (Fig. 1).
What is the diagnosis?
The peripheral blood smear shows neutrophilic leukocytosis with granulocytes at different stages of maturation including myeloblasts, myelocyte, metamyelocytes, bands, and mature neutrophils. This is characteristic of chronic myeloid leukemia (CML). Bone marrow biopsy confirmed the diagnosis with conventional cytogenetics showing Philadelphia chromosomes.
CML is a myeloproliferative neoplasm characterized by translocation t(9;22) giving rise to a constitutively-activated tyrosine kinase BCR-ABL which drives aberrant WBC proliferation. CML leads to production of mature functioning WBCs and hence these patients typically do not present with infections and instead have fatigue and symptoms of splenomegaly e.g. early satiety, or LUQ pain, particularly when bending down e.g. tying their shoes. Differential diagnoses include leukemoid reaction, other myeloproliferative disorders, chronic myelomonocytic leukemia and proliferative myelodysplastic syndromes. Diagnosis is confirmed with detection of Philadelphia chromosomes, which however may be negative in 10–15% cases [