What are the cytogenetic characteristics, lymphocyte morphology, and immunophenotypes of Burkitt's Leukemia?

Burkitt's Leukemia: Cytogenetics, Morphology, and Immunophenotype

Burkitt's leukemia is definitively characterized by MYC gene rearrangement, most commonly t(8;14)(q24;q32) or its variants t(2;8) and t(8;22), with the critical diagnostic requirement being absence of BCL2 or BCL6 rearrangements and lack of complex karyotype. 1

Cytogenetic Characteristics

Primary Translocation

• The hallmark cytogenetic abnormality is t(8;14)(q24;q32), which juxtaposes the MYC oncogene at 8q24 to the IGH locus at 14q32 1
• Variant translocations occur in approximately 10-15% of cases: t(2;8)(p12;q24) involving IGK-MYC and t(8;22)(q24;q11.2) involving IGL-MYC 1, 2
• The defining feature that distinguishes true Burkitt's from other aggressive B-cell lymphomas is the presence of MYC rearrangement WITHOUT additional involvement of BCL2 or BCL6 and WITHOUT complex karyotype 1

Secondary Chromosomal Abnormalities

• Approximately 40% of Burkitt's cases have the IG-MYC fusion as the sole abnormality, representing the purest form of the disease 3
• When secondary abnormalities occur, they include gains at chromosomes 1q, 7, and 12, and losses of 6q, 13q32-34, and 17p 3, 4
• The presence of high cytogenetic complexity (multiple nonspecific abnormalities) should prompt critical review of the diagnosis, as this suggests an alternative aggressive B-cell lymphoma rather than true Burkitt's 3
• Dual translocations of chromosome 14 are extremely rare, though cases with both t(8;14) and additional chromosome 14 rearrangements have been reported 2

Critical Diagnostic Pitfall

• Cases with MYC rearrangement PLUS BCL2 or BCL6 translocations ("double-hit" or "triple-hit" lymphomas) are NOT Burkitt's leukemia and should be classified as high-grade B-cell lymphoma 1, 5
• These double/triple-hit cases require FISH testing with IGH, BCL2, and BCL6 probes for proper classification and have significantly worse prognosis requiring more intensive therapy 1, 5

Lymphocyte Morphology

Blast Cell Characteristics

• Burkitt's leukemia blasts display classic FAB L-3 morphology: medium-sized cells with round nuclei, finely stippled chromatin, multiple small nucleoli (2-5), and deeply basophilic cytoplasm 6
• The cytoplasm contains prominent lipid vacuoles that are typically numerous and evenly distributed throughout the cell 6
• Cells are remarkably uniform in size and appearance, creating a monotonous morphologic pattern 3, 6

Proliferation Index

• A near-100% proliferation fraction (Ki-67 ≥95%) is characteristic and essentially required for diagnosis 1, 5, 3
• Ki-67 index below 95% should raise suspicion for diffuse large B-cell lymphoma or intermediate lymphoma rather than true Burkitt's 5
• This extremely high proliferation rate reflects the aggressive nature and rapid doubling time of the disease 1, 3

Morphologic Variants and Pitfalls

• Some cases may show "Burkitt-like" morphology with mature B-cell phenotype but proliferative fractions approaching 100% even without proven MYC translocation 1
• The combination of Burkitt's morphology with precursor B-cell immunophenotype represents a diagnostic pitfall that can delay proper management 6
• Proper morphologic/immunophenotypic correlation is essential, with awareness that overlapping features can occur 6

Immunophenotype

Classic Immunophenotype Profile

• CD45: bright positive (distinguishes from precursor B-ALL which is dim) 6
• CD20: bright positive (strong B-cell marker expression) 1, 6
• CD10: positive (germinal center marker) 1, 3, 6
• CD19: positive (pan B-cell marker) 1, 6
• Surface immunoglobulin (sIg): positive with light chain restriction (kappa or lambda) 1, 6
• Terminal deoxynucleotidyl transferase (TdT): negative (critical for excluding precursor B-ALL) 6

Additional Markers for Diagnosis

• BCL6: positive (germinal center origin) 3
• BCL2 protein: negative or very weak expression (critical distinguishing feature) 5, 3
• CD5: negative 1
• CD23: variable, typically negative or dim 1
• Cyclin D1: negative (excludes mantle cell lymphoma) 1

Diagnostic Algorithm for Immunophenotyping

1. First, confirm mature B-cell lineage: CD20 bright positive, CD19 positive, surface Ig positive with light chain restriction 1, 6
2. Second, exclude precursor B-ALL: TdT must be negative, CD45 must be bright (not dim) 6
3. Third, confirm germinal center origin: CD10 positive, BCL6 positive 1, 3
4. Fourth, exclude other lymphomas: BCL2 protein negative/very weak, cyclin D1 negative 1, 5, 3
5. Fifth, assess proliferation: Ki-67 must be ≥95% 5, 3

Atypical Immunophenotypes

• Rare cases may be CD10-negative, though this should prompt careful review of the diagnosis 1
• When atypical immunophenotype is encountered (such as TdT positivity with Burkitt morphology), cytogenetic confirmation with MYC translocation becomes absolutely essential 6
• Cases with BCL2 positivity by immunohistochemistry exclude Burkitt's diagnosis and favor high-grade B-cell lymphoma or DLBCL 5

Integration of Diagnostic Criteria

The diagnosis of Burkitt's leukemia requires concordance of all three elements: proven IG-MYC translocation without BCL2/BCL6 rearrangements or complex karyotype, classic morphology with ≥95% Ki-67, and mature B-cell immunophenotype with CD10+/BCL6+/BCL2 protein negative or very weak 1, 3. Any discordance among these features necessitates consideration of alternative diagnoses such as high-grade B-cell lymphoma with MYC rearrangement, DLBCL, or precursor B-ALL 5, 3, 6.