Mixed-phenotype acute leukemias are rare acute leukemias that has an ambiguous pattern of antigen expression. This may constitute a population of blast with multiple antigens of different lineages expressed on the same cell (biphenotype) or different population each expressing antigen of a different lineage (bilineage). MPAL generally have a poor prognosis.

Bone marrow aspirate from a patient with mixed phenotype acute leukaemia showing two clear blast populations. The first is small with an extremely high nuclear-cytoplasmic ratio, 1-2 prominent nucleoli and an occasional hand-mirror appearance. These are lymphoblasts. The second is larger, with more irregular nuclei, multiple nucleoli and a higher nuclear-cytoplasmic ratio. These are myeloblasts.

Diagnostic Criteria (WHO 2016)

The diagnosis of mixed phenotype acute leukaemia relies on immunophenotyping. Requirements for lineage assignment include:

1) Myeloid Lineage

  • MPO (by flow cytometry, immunohistochemistry, or cytochemistry) or
  • Monocytic differentiation (≥ 2 of the following: non-specific esterase, CD11c, CD14, CD64 or lysozyme)

2) T-cell lineage

  • Cytoplasmic CD3 (by flow cytometry with antibodies to CD3 epsilon chain. Immunohistochemistry using polyclonal anti-CD3 antibody may detect CD3 zeta chain, which is not T-cell-specific) or
  • Surface CD3 (rare in mixed-phenotype acute leukaemias)

3) B-cell lineage (multiple antigens required)

  • Strong CD19 with ≥1 of the following strongly expressed: CD79a, cytoplasmic CD22, CD10 or
  • Weak CD19 with ≥2 of the following strongly expressed: CD79a, cytoplasmic CD22, CD10
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Peripheral blood films from two patients with mixed phenotype acute leukemia. There are a significant number of circulating blasts. Most are morphologically lymphoblasts but there is a separate population of larger blasts which are more myeloid in appearance. Correlation with immunophenotyping is required for diagnosis.

Blood Film Features:

  • Blast features may be undifferentiated or dimorphic
    • Undifferentiated blast population: no morphologically differentiated features
    • Dimorphic blast population: some blasts resembling myeloblasts or monoblasts and some resembling lymphoblasts
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Bone marrow aspirates from two patients with mixed phenotype acute leukaemia.

Bone Marrow Features:

  • Blast population: as described above
  • Cytochemistry: MPO or non-specific esterase to delineate myeloid lineage

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