What is the significance of metamyelocytes in the peripheral blood?

Metamyelocytes in Peripheral Blood

Clinical Significance

The presence of metamyelocytes in peripheral blood represents an abnormal "left shift" indicating premature release of immature granulocytic precursors from the bone marrow, which may signal myelodysplastic syndromes, myeloproliferative neoplasms, bone marrow infiltration, or severe reactive processes such as infection or inflammation. 1

Metamyelocytes are immature granulocytic cells that normally complete their maturation within the bone marrow before being released as mature neutrophils. 1 Their appearance in peripheral circulation is always pathological and warrants systematic evaluation. 1

Differential Diagnosis

Myelodysplastic Syndromes (MDS)

• Peripheral blood dysplasia including immature myeloid cells like metamyelocytes is a key diagnostic feature of MDS according to WHO classification. 2, 1
• Dysplastic metamyelocytes may demonstrate abnormal nuclear configuration (pseudo Pelger-Huet anomaly), nuclear hypersegmentation, or cytoplasmic hypogranulation/degranulation. 2
• The presence of dysplastic cells in peripheral blood is an important criterion for diagnosing various MDS subtypes. 1

Myeloproliferative/Myelodysplastic Overlap Syndromes

• Chronic myelomonocytic leukemia (CMML) frequently presents with circulating metamyelocytes and other immature myeloid cells (IMC). 2
• The presence of IMC in peripheral blood was identified as an independent prognostic variable in CMML, associated with shorter survival. 2
• Atypical chronic myeloid leukemia may also present with significant numbers of circulating metamyelocytes. 1

Reactive Causes

• Severe infections trigger significant left shift with metamyelocytes in peripheral blood, representing enhanced bone marrow activity in response to systemic inflammation. 3, 4
• Band cells >10% of white blood cells had 84% sensitivity and 71% specificity for detecting definite sepsis in critically ill patients. 4
• Other reactive causes include severe inflammation, tissue necrosis, and hemorrhage. 1

Diagnostic Approach

Initial Laboratory Evaluation

• Obtain complete blood count with manual differential to assess for cytopenias, determine the percentage and absolute count of metamyelocytes, and identify other immature cells. 1
• Evaluate for presence of blasts, which would suggest more advanced disease (MDS-2 or acute leukemia). 2

Peripheral Blood Smear Examination

• Carefully examine for dysplastic features in all three cell lines (erythroid, myeloid, megakaryocytic). 2, 1
• Look for granulocyte nuclear hypolobation (pseudo Pelger-Huet), cytoplasmic hypogranulation/degranulation, and bizarre nuclear shapes. 2
• Assess erythrocytes for anisocytosis, poikilocytosis, and basophilic stippling. 2
• Evaluate platelets for anisocytosis and giant forms. 2

Bone Marrow Examination Indications

Bone marrow examination is mandatory when persistent unexplained cytopenias or suspicion of hematologic malignancy exists. 2, 1

The evaluation must include:

• Bone marrow aspirate with assessment of dysplasia in all hematopoietic cell lines, enumeration of blasts, and ring sideroblasts. 2
• Bone marrow biopsy to assess cellularity, CD34+ cells, fibrosis, and megakaryocytic dysplasia. 2
• Cytogenetic analysis (mandatory) to detect acquired clonal chromosomal abnormalities for diagnosis and prognostic assessment. 2
• Next-generation sequencing for mutation analysis, particularly SF3B1 and TP53 for classification, and expanded panels for IPSS-M prognostic scoring. 2

Critical Diagnostic Criteria

• To qualify as significant dysplasia in MDS, >10% of nucleated cells in the affected lineage must demonstrate dysplastic features. 2
• Count at least 200 cells in blood smears and 500 cells in bone marrow smears, including at least 100 erythroblasts and 30 megakaryocytes. 2

Prognostic Implications

In Myelodysplastic Syndromes

• The presence of immature myeloid cells in peripheral blood was identified as an independent adverse prognostic factor in CMML, associated with shorter median survival. 2
• The degree of dysplasia and presence of immature cells correlates with disease severity and prognosis. 1

In Severe Infections

• Patients who died within 1 week had significantly higher levels of myelocytes and metamyelocytes (median 9%) compared to those who died at 2-4 weeks (median 0.5%), suggesting prognostic value for short-term mortality. 4
• Immature granulocyte counts were independently associated with intubation and mortality in COVID-19 patients. 3

Clinical Pitfalls to Avoid

• Do not exclude MDS based solely on the presence of leukocytosis; MDS/MPN overlap syndromes frequently present with elevated white blood cell counts. 5
• Transient appearance of metamyelocytes can occur in severe infections and should resolve with treatment of the underlying condition. 1
• If only unilineage dysplasia is present without increased blasts or specific cytogenetic abnormalities, observation for 6 months with repeat evaluation is recommended before diagnosing MDS. 6
• Avoid premature diagnosis of MDS without complete evaluation including cytogenetics and molecular testing. 6
• Persistent circulation of metamyelocytes without obvious reactive cause warrants close follow-up, as it may represent early manifestation of a myeloid neoplasm. 1

Special Consideration: Vitamin B12/Folate Deficiency

• Giant metamyelocytes with megaloblastic features can occur in pernicious anemia and other megaloblastic states. 7, 8
• These cells show increased nuclear and cytoplasmic size with abnormal nuclear-cytoplasmic ratios. 7
• This diagnosis should be excluded by checking vitamin B12 and folate levels before pursuing bone marrow evaluation for suspected MDS. 6