What is the diagnosis for a patient with a bone marrow sample showing 57% blasts, hypercellular marrow, and immunophenotypic profile positive for myeloid markers (Myeloperoxidase (MPO)), CD13, CD33, CD117, CD7, CD34, and HLA-DR (Human Leukocyte Antigen-DR), and a phenotype of Acute Myeloid Leukemia (AML) with aberrant CD7 expression?

Diagnosis: Acute Myeloid Leukemia (AML) with Aberrant CD7 Expression

This patient has Acute Myeloid Leukemia (AML), specifically AML-M4 (acute myelomonocytic leukemia) by FAB classification, confirmed by bone marrow morphology showing 57% blasts in a hypercellular marrow with positive myeloid markers (MPO, CD13, CD33, CD117) and characteristic aberrant CD7 expression. 1

Diagnostic Confirmation

The diagnosis is definitively established by:

• Blast percentage of 57% exceeds the WHO threshold of ≥20% blasts required for AML diagnosis 1, 2
• Positive myeloperoxidase (MPO) confirms myeloid lineage, which is the gold standard myeloid marker 1
• Expression of multiple myeloid markers (CD13, CD33, CD117) with precursor markers (CD34, HLA-DR) is consistent with AML immunophenotype 1, 3
• Hypercellular bone marrow with 57% blasts on morphologic examination of bone marrow aspirate is the diagnostic gold standard 2

Significance of Aberrant CD7 Expression

The aberrant CD7 expression is a lineage-aberrant antigen that does not change the diagnosis but has important prognostic and monitoring implications:

• CD7 is classified as a lineage aberrant antigen in AML, representing T-cell marker expression on myeloid blasts 1
• Aberrant CD7 expression occurs in approximately 73% of AML cases and is useful for minimal residual disease (MRD) monitoring 4, 3
• AML with t(4;12) frequently shows aberrant CD7 expression and is associated with aggressive disease, though this specific translocation must be confirmed by cytogenetics 4

Critical Next Steps for Complete Diagnosis

Molecular and cytogenetic testing is mandatory and must be completed before finalizing risk stratification:

• Cytogenetic analysis is mandatory for proper classification, prognosis, and treatment decisions 1
• Molecular testing for FLT3-ITD, NPM1, and CEBPA mutations is essential for risk stratification, particularly in patients with normal karyotype 1
• These results will determine whether this is favorable-risk (e.g., NPM1 mutation without FLT3-ITD), intermediate-risk, or adverse-risk AML 1

Important Diagnostic Considerations

The immunophenotypic profile requires careful interpretation:

• The presence of B-lineage positivity mentioned in the sample requires clarification—true Mixed Phenotype Acute Leukemia (MPAL) requires strong CD19 expression with at least one of intracellular CD79a, intracellular CD22, or CD10 1
• If B-lineage markers are weakly positive or represent only CD19 without additional B-cell markers, this remains AML with aberrant antigen expression rather than MPAL 1
• The T-lineage marker CD7 alone does not establish T-lineage involvement—MPAL with T-lineage requires intracellular CD3 or surface CD3 1

Prognostic Implications

Risk stratification depends entirely on pending cytogenetic and molecular results:

• Favorable cytogenetics include t(8;21), inv(16), or t(15;17), each occurring in 5-10% of AML cases 1
• Adverse cytogenetics include inv(3), t(3;3), t(6;9), or monosomy 7, which would significantly worsen prognosis 1, 5
• FLT3-ITD mutation (present in 20-40% of AML) confers adverse prognosis, while NPM1 mutation without FLT3-ITD is favorable 1

MRD Monitoring Strategy

The aberrant CD7 expression provides an excellent marker for minimal residual disease monitoring:

• Flow cytometry using the aberrant CD7 expression pattern can detect residual disease below morphologic thresholds 6, 3
• MRD monitoring should be performed at specific timepoints: after induction, after consolidation, and before any stem cell transplantation 1, 6
• Negative flow cytometry with ≥5% morphologic blasts may indicate regenerating marrow rather than residual disease, requiring repeat assessment 6

Common Pitfalls to Avoid

• Do not rely on peripheral blood flow cytometry alone—bone marrow aspirate with morphologic examination of at least 500 nucleated cells is mandatory 2
• Do not substitute flow cytometry for morphologic blast counting, as flow cytometry has detection thresholds (typically 20% positivity) that may miss populations 2
• Do not finalize risk stratification or treatment planning until cytogenetic and molecular results are available 1
• Be aware that immunophenotypic shifts can occur at relapse in up to 92% of cases (11/12 in one series), requiring repeat immunophenotyping 6