Significance of Immature Myeloid Cells in Peripheral Blood
This peripheral blood smear showing 33% immature myeloid cells (3% promyelocytes, 13% myelocytes, 17% metamyelocytes) represents a pathological "left shift" that is highly concerning for a myeloproliferative neoplasm, most likely chronic myeloid leukemia (CML), and requires immediate bone marrow examination with cytogenetic analysis to establish the diagnosis. 1
Clinical Significance
The presence of this degree of immature granulocytes in peripheral blood is abnormal and indicates:
Granulocytic proliferation with left-shifted forms is characteristic of myeloproliferative neoplasms, particularly CML and primary myelofibrosis (PMF), where prominent granulocyte proliferation with left-shifted forms is typical 1
CML characteristically presents with unregulated growth of myeloid cells resulting in abnormally high levels of differentiated granulocytes and granulocytic precursor cells in the blood, creating this "pathological shift to the left" 1
The combined percentage of immature forms (33%) far exceeds what would be seen in reactive conditions and strongly suggests a clonal myeloid disorder 2
Immediate Diagnostic Workup Required
Bone marrow examination is mandatory and should include:
Bone marrow aspirate for morphology with blast percentage, promyelocyte percentage, and assessment of dysplasia 1
Karyotyping on bone marrow cells to identify the Philadelphia chromosome t(9;22)(q34;q11) which is diagnostic of CML, as well as additional cytogenetic abnormalities 1
Molecular testing with RT-PCR to detect BCR::ABL1 transcript if CML is suspected 1
Complete blood count with differential including assessment for basophilia (which is characteristic of CML), anemia, and platelet count 1
Differential Diagnosis Considerations
The main diagnostic considerations include:
Chronic Myeloid Leukemia (CML): Most likely diagnosis given the marked left shift. CML-chronic phase is characterized by high leukocyte counts with this pattern of immature cells 1, 3
Primary Myelofibrosis (PMF): Also presents with prominent granulocyte proliferation with left-shifted forms, but typically accompanied by leukoerythroblastosis (nucleated red blood cells), teardrop cells, anemia, and splenomegaly 1, 2
Reactive left shift: While infections and inflammatory conditions can cause immature granulocytes, the degree seen here (33% combined) is excessive for a reactive process 4
Critical Pitfalls to Avoid
Do not delay bone marrow examination: Even when peripheral blood findings are suggestive, bone marrow evaluation with cytogenetics is essential for definitive diagnosis and to exclude other myeloid neoplasms 1, 2
Assess blast percentage carefully: While this case shows only 3% promyelocytes, ensure accurate blast enumeration as ≥20% blasts would indicate blast phase disease requiring different management 1, 5
Evaluate for dysplasia: Prominent dyspoiesis can occur in CML (particularly accelerated phase) and may mimic myelodysplastic syndromes, making cytogenetic analysis critical 3, 6
Check basophil count: Absence or near-absence of basophils in the setting of marked left shift can represent an atypical presentation of CML and should not exclude the diagnosis 3
Additional Laboratory Assessment
Beyond the mandatory bone marrow examination, obtain:
Serum lactate dehydrogenase (LDH): Elevated in myeloproliferative disorders 1
Peripheral blood smear review: Look for teardrop cells (suggesting myelofibrosis), basophilia (supporting CML), and assess red blood cell morphology 1, 2
Flow cytometry can help characterize the immature myeloid population and assess for aberrant antigen expression patterns, though morphology and cytogenetics remain primary diagnostic tools 6