Leukemia - Acute
Other ALL
Ambiguous Lineage

Author: Daniela Mihova, M.D. (see Authors page)

Revised: 13 April 2018, last major update September 2012

Copyright: (c) 2001-2018, PathologyOutlines.com, Inc.

PubMed Search: Acute leukemias of ambiguous lineage [title]

Cite this page: Mihova, D. Ambiguous Lineage. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/leukemiaambiguouslin.html. Accessed August 17th, 2018.
Definition / general
  • Acute leukemias in which the morphologic, cytochemical and immuno-phenotypic features of the blasts:
    • Lack sufficient evidence to classify as myeloid or lymphoid origin
    • Or, have morphologic and / or immunophenotypic characteristics of both myeloid and lymphoid cells
    • Or, have both B and T lineages (acute bilineal leukemia and acute biphenotypic leukemia)

    Acute leukemias of ambiguous lineage include the following:
    • Acute undifferentiated acute leukemia
    • Mixed phenotype acute leukemia with t(9;22)(q34;q112.); BCR-ABL1
    • Mixed phenotype acute leukemia with t(v;11q23); MLL rearranged
    • Mixed phenotype acute leukemia, B/myeloid, NOS
    • Mixed phenotype acute leukemia, T/myeloid, NOS
    • Mixed phenotype acute leukemia, NOS rare types
    • Other acute leukemias of ambiguous lineage
Epidemiology
  • < 4% of all acute leukemias, more frequent in adults
Etiology
  • Unknown
Clinical features
  • Related to bone marrow failure: fatigue, infections, bleeding
Morphology
  • Acute undifferentiated leukemia
    • Leukemic cells lack any differentiating features
  • Acute biphenotypic and acute bilineal leukemias
    • May present as one subtype of AML with features of ALL (B, T or B and T)
Immunophenotype
Undifferentiated acute leukemia:
  • Leukemias lack specific lineage markers
  • cCD79a, cCD22, CD3 and MPO
  • Generally don’t express more than one lineage associated marker
  • Often express HLA-DR, CD34, CD38, may express TdT and CD7

Bilineal acute leukemia
Biphenotypic acute leukemia
  • Blasts co-express myeloid and T or B lineage markers
  • Or, concurrent B and T lineage markers
  • Rarely co-express markers for myeloid, T and B lineages

  • Co-expression of one or two cross-lineage (nonspecific) markers is not sufficient for biphenotypic leukemia; e.g. myeloid antigen positive ALL or Lymphoid antigen positive AML
  • Lineage switch after therapeutic intervention
    • Possible expansion of pre-existing minor population of blasts of different lineage following therapeutic suppression of the major population
    • Possible lineage instability
Genetics
  • High degree of cytogenetic abnormalities
  • 1/3 of cases have Ph chromosome
  • t(4;11)(q21;q23) or 11q23, typically have CD10(–) precursor B lymphoid component
  • T/myeloid biphenotypic or bilineal leukemia can have complex karyotype
Cell of origin
  • Multipotent progenitor stem cell
Prognostic factors
  • Unfavorable, particularly in adults
  • t(4;11) or Ph particularly unfavorable
Treatment
  • Usually aggressive chemotherapy or bone marrow transplant
Case reports
Microscopic (histologic) images

Images hosted on PathOut server:

Blood smears:
Missing Image

Child with t(4;11)(q21;q23) - small blasts are early B cell precursors that are CD10 negative,
large cells are monocyte precursors that are alpha naphthyl butyrate esterase+



Bone marrow smears:
Missing Image

2 week old girl with t(4;11)(q21;q23)
- lymphoblasts and monoblasts

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2 week old girl with t(4;11)(q21;q23) - Large
cells are monoblasts and promonocytes,
small cells are lymphoblasts with minimal
cytoplasm and coarse chromatin



Images hosted on other servers:

Blood smears:
Missing Image

Blasts have minimal cytoplasm, fine chromatin with 1+ prominent nucleoli



Bone marrow smears:
Missing Image

Myeloid features include Auer rod (fig 1A-asterisk) and myeloperoxidase staining (fig 1B)

Flow cytometry Images

Images hosted on other servers:
Missing Image

Biphenotypic acute leukemia with CD19 and myeloperoxidase coexpression (figure B)

Electron microscopy images

Images hosted on PathOut server:
Missing Image

Monocytoid blast has folded nucleus and scattered small electron dense granules

Molecular / cytogenetics description
  • Many cases have IgH and TCR rearrangements or deletions
Differential diagnosis
  • For biphenotypic acute leukemia
    • Myeloid antigen positive ALL
    • Lymphoid antigen positive AML
  • For undifferentiated acute leukemia