Case Study Hematology Interest

Case History: A 45-year-old male presents to the ER with night sweats and generalized fatigue. He is currently undergoing treatment with Ara-C for Chronic Myeloid Leukemia.
Laboratory CBC with Differential: WBC=133 x10^3/uL, MCV=84 fL, HGB=8.7 g/dL, PLT=55 x10^3/uL Pathologist Interpretation: The peripheral blood morphology shows a dramatic left shift that extends down to the promyelocyte stage and occasional blast. There is also mild basophilia & eosinophilia. There is moderate red cell poikilocytosis including tear drops.

Platelet Morphology: Abnormal Platelets, Micromegakaryocytes, and Megakaryocytic Fragments are Present.

The clinical picture of increased leukocyte count and splenomegaly raise concern for chronic myelogenous leukemia. Bone marrow aspiration was obtained and shown below.


Pathologist Interpretation: Bone marrow aspirate and biopsy are of good quality for interpretation. The particles are hypercellular. There is moderate dyserythropoiesis with nuclear-cytoplasmic asynchrony, irregular nuclear contours and nuclear budding. Granulopoiesis is hyperplastic but blasts are not increased. The ME ratio is 9:1. Megakaryocytes are reduced in number and consist mainly of small forms. Scattered sea-blue histiocytes are seen. The biopsy is markedly hypercellular (nearly 100%) with prominent granulocytic hyperplasia. Reticulin stain shows minimal reticulin fibrosis (grade 1/3).



Result: 46,XY,t(9;22)(q34;q11.2)[25]

The presence and expansion of BCR-ABL is the defining feature of CML. This fusion gene codes for an abnormal protein with Tyrosine Kinase which increases cell proliferation by transferring a phosphate group from ATP to intracellular proteins that regulate cell division; resulting in overgrowth. Most cases have the characteristic t(9;22)(q34;q11.2) identified by routine cytogenetic analysis.


Chronic Myeloid Leukemia (CML)

Blood, bone marrow aspirate and biopsy consistent with chronic myeloid leukemia, likely accelerated phase.

Segmented neutrophils, bands, metamyelocytes, and myelocytes predominate, and immature and mature eosinophils and basophils are increased. Myeloblasts and promyelocytes are present at a rate of approximately 1% and 5% respectively.

The increasing white cell count and decreasing platelet count would be consistent with accelerated phase of CML if other causes are excluded. Monocytes are increasing, and it is noted they were elevated in 2006. There is moderate dyserythropoiesis and decreased megakaryocytes which have been reported previously. Possible causes include therapy-related change or cytogenetic evolution. There is no evidence of blast crisis.

Educational discussion

Chronic Myeloid Leukemia - Peripheral Blood

Chronic myeloid leukemia (CML) is a myeloproliferative disorder arising from a single genetic translocation in a pluripotential hematopoietic stem cell producing a clonal overproduction of the myeloid cell line. CML is characterized by marked leukocytosis, basophilia, and a dramatic left shift with a predominance of myelocytes, myeloid bulge.

CML has three phases a chronic clinical phase, accelerated phase, and terminates as an acute leukemia in the blast phase. The Philadelphia chromosome is associated in virtually all cases (95%) of CML and must be identified to confirm the diagnosis.

CML is primarily a disease of adults and is predominantly in males over 70 years of age. Symptoms associated are usually minimal and include fatigue, anorexia, abdominal bloating, weight loss, night sweats, dyspnea, pallor, spontaneous bleeding, lymphadenopathy, hepatomegaly, and blurry vision. Some patients are asymptomatic and diagnosis is made incidentally during routine blood testing.

CML can progress to a blast phase defined by >20% blasts in the peripheral blood or bone marrow or by an extramedullary blast proliferation. The blast lineage may be myeloid or lymphoid.

Chronic Myeloid Leukemia - Bone Marrow

Hypercellularity with a very high Myeloid:Erythroid ratio (up to 50:1) and an increase in neutrophils and neutrophil precursors as a result of increased production of myeloid cells. Normoblasts appear reduced in number. Megakaryocytes are normal or increased in number, may appear in clusters, and are often small with reduced nuclear size and reduced nuclear lobulations ("dwarf megakaryocytes"). Reticulin fibers can be increased and the presence of pseudo-Gaucher cells are common and are associated with intramedullary cell destruction.

Pseudo-Gaucher cells and sea-blue histiocytes can be seen due to increased cell turnover. The macrophage cytoplasm is filled with insoluble lipid pigment, called ceroid, which is thought to represent partially digested globosides derived from cell membranes. As compared to Gaucher cells, these cells stain more intensely blue with Wright-Giemsa and the inclusions are globular rather than fibrillary.



The Philadelphia chromosome resulting from t(9;22) creates a chimeric fusion gene BCR-ABL. The presence and expansion of BCR-ABL is the defining feature of CML, as well as the underlying pathophysiologic abnormality of CML. Ph chromosome resulting from t(9;22) is detected in 90% - 95% of cases.


  1. Rodak, Bernadette F., George A Fritsma, and Elaine M Keohane. Hematology: Clinical Principles and Applications. 5th ed. St. Louis, Mo.: Elsevier Saunders, 2016.
  2. Cancer Genet Cytogenet. 2007;173(2):97, Br J Haematol. 2004;125(2):187
  3. Pasternak G, Hochhaus A, Schultheis B, Hehlmann R. Chronic myelogenous leukemia: molecular and cellular aspects. J Cancer Res Clin Oncol. 1998;124(12):643-60. doi: 10.1007/s004320050228. PMID: 9879825
  4. https://imagebank.hematology.org/reference-case/37/chronic-myelogenous-leukemia-bcrabl1-positive
  5. Thompson, P. A., Kantarjian, H. M., & Cortes, J. E. (2015). Diagnosis and Treatment of Chronic Myeloid Leukemia in 2015. Mayo Clinic proceedings, 90(10), 1440–1454. https://doi.org/10.1016/j.mayocp.2015.08.010
  6. Zhang S., Davidson D.D., Cheng L. (2013) Clinical Molecular Biology: Principles. In: Cheng L., Zhang D., Eble J. (eds) Molecular Genetic Pathology. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-4800-6_2
  7. https://beyondthedish.wordpress.com/tag/philadelphia-chromosome/
  8. https://imagebank.hematology.org/imageset/595/pseudogaucher-cells

Test your knowledge and take the CML Quiz.

Check out our Website!

Created By
Hematology Interest


Acknowledgement: Virtual slide provided here with the permission from the Department of Hematopathology, Vancouver General Hospital, Vancouver, BC, Canada.