Category Archives: Acute Leukemia

Organ Systems, Bone Marrow, WHO Classification, Hematopathology, Acute Leukemia

Acute Undifferentiated Leukemia

A vary rare acute leukemia that does not express markers considered specific for lineage determination. (e.g. MPO, esterase, cCD3, cCD22, strong CD19, etc.).  Typically there will be one or less lineage markers for any lineage.  CD34, HLA-DR, and TdT may be expressed, but are not specific for any lineage.
 

Care should be taken that immunophenotyping panels are extensive, and consideration is given to other entities such as plasmacytoid dendritic precursors, non-hematopoietic tumors, NK-cell precursors, etc.  Essentially, a diagnosis of exclusion.

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Organ Systems, Bone Marrow, WHO Classification, Hematopathology, Acute Leukemia

Myeloid/Lymphoid Neoplasms Associated with Eosinophilia

  • PDGFA
    • Eosinophilia with increased tryptase and marrow mast cells
    • Cryptic deletion in chromosome 4q12
    • FIP1L1-PDGFA, many other partners
    • Responsive to tyrosine kinase inhibitors (e.g. imatimib/Gleevec®)
  • PDGFB
    • Eosinophilia combined with monocytosis that mimics CMML
    • t(5;12)(q31;33;p12) ETV6-PDGFB, many other partners
    • Responsive to TKIs 
  • FGFR1
    • Eosinophilia combined with AML or T-ALL
    • Associated with 8p11 translocations, FGFR1 with multiple partners
    • Not responsive to TKIs (poor prognosis)
  • PCM1-JAK2 (provisional entity)
    • Eosinophilia along with acute lymphoblastic leukemia (B-cell) or lymphoma (T-cell)
    • Bone marrow with lymphoid aggregates and increased/left shifted erythroid precursors (mimics PMF)
    • May respond to JAK2 inhibitors (e.g ruxolitinib/Jakafi®)
References

Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127: 2391–2405. doi:10.1182/blood-2016-03-643544

Swerdlow SH, Campo E, Harris, NL, Jaffe ES, Pileri SA, Stein H, Thiele J (Eds):  WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (Revised 4th edition). IARC: Lyon 2017

Organ Systems, WHO Classification, Hematopathology, Acute Leukemia

WHO 2008/2016 Criteria for Mixed-Phenotype Blasts

Myeloid

  • MPO expression (flow cytometry, immunohistochemistry, or enzyme cytochemistry) – WHO does not define thresholds for positiivity, which can result in variability between laboratories
    • Flow cytometry:  >10% (some propose 13%) expression compared to isotype control (preferred methodology)
    • Enzyme cytochemsitry:  >3% staining of blasts
    • IHC:  No well-defined cutoff (not commonly done – MPO IHC is available)

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Organ Systems, Bone Marrow, WHO Classification, Hematopathology, Acute Leukemia

EGIL Algorithm for Biphenotypic Blasts

European Group for the Immunological Characterization of Leukemias (EGIL) algorithm for biphenotypic blasts. 
Points
B
T
Myeloid
2
cyCD79a
CD3 (cy or sm)
MPO
 
cyCD22
TCR-αβ
 
 
cyIgM
TCR-γδ
 
1
CD19
CD2
CD117
 
CD20
CD5
CD13
 
CD10
CD8
CD33
 
 
CD10
CDw65
0.5
TdT
TdT
CD14
 
CD24
CD7
CD15
 
 
CD1a
CD64

Biphenotypic leukemia is defined as a score >2 in 2 lineage columns.

WHO 2008/2016 Criteria for Mixed-Phenotype Blasts
Mixed Phenotypic Acute Leukemias (MPAL)
References

Bene MC, Castoldi G, Knapp W, et al. Proposals for the immunological classification of acute leukemias: European Group for the Immunological Characterization of Leukemias (EGIL). Leukemia. 1995;9(10):1783–1786

 

 

Organ Systems, Bone Marrow, Hematopathology, Acute Leukemia

MPAL

Mixed Phenotype Acute Leukemia (MPAL) comprises either blasts with myeloid and lymphoid expression or leukemia with a mixture of myeloblasts and lymphoblasts.
  • BIPHENOTYPIC – single population of blasts that express key markers of different lineages (e.g. T-ALL, B-ALL, and/or AML).
  • BILINEAL – two cell populations each diagnostic of separate acute leukemia lineages (combined populations ≥20% blasts to met threshold for acute leukemia).

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