A 38-year-old male with Asperger’s is found to have the following abnormalities on routine blood work. He has no other symptoms or relevant medical history.
- What is your differential diagnosis?
- What genetic mutation is responsible for this acquired malignancy?
Click for answer:
Diagnosis: Chronic myeloid leukemia (CML)
CBC Clues:
(1) Leukocytosis with predominant neutrophilia
(2) Basophilia
(3) Myeloid precursors (metamyelocytes, bands)
Q1: What is your differential diagnosis?
CML, CNL, infection, polycythemia vera, drugs (see Box)
Q2: What genetic mutation is responsible for this acquired malignancy?
t(9;22) or Philadelphia chromosome
Differential for “Left Shift”
• CML
• CNL (chronic neutrophilic leukemia)
• Infection
• Polycythemia vera
• Drugs
CBC Pearls
• Basophilia is a hallmark finding of CML
• BCR-ABL testing is the diagnostic test of choice
CML is a hematologic malignancy of the myeloid lineage. It is characterized by a translocation of chromosomes 9 (ABL) and 22 (BCR), resulting in the BCR/ABL fusion gene. This is sometimes referred to as t(9;22) or the Philadelphia chromosome. Like other myeloproliferative neoplasms, CML has a risk of progressing to an acute leukemia. Disease stages are thus divided into three phases: chronic, accelerated, and blast phase. Patients often present in the chronic phase with symptoms of anemia and splenomegaly.
The CBC will reflect neutrophil proliferation and immature cells (bands, metamyelocytes in this case). The presence of immature myeloid cells is sometimes referred to as a “left shift”. Basophils and eosinophils are also commonly increased and should raise suspicion for CML.
Treatment for CML has been revolutionized by tyrosine-kinase inhibitors which have significantly reduced mortality. These drugs target the tyrosine kinase enzyme that is responsible for cell proliferation in CML. Examples include imatinib (first generation) and dasatinib (second generation).